Wiki Operation Log

[2026-06-29] ingest | Morra ME 2018 - Defining Warning Signs and Severe Dengue

Created (1): sources/Morra2018 - Defining Warning Signs and Severe Dengue.md (Rev Med Virol; PRISMA systematic review of how 44 WHO-2009 studies operationally define the warning-sign / severe-dengue signs — only 2 of 16 signs (liver enlargement; liver involvement = AST/ALT >1000) reach consensus, both WHO-2009-predefined; “shock” defined 23 distinct ways). Updated (6): index.md (Sources 21→22, total 106→107 — sections still sum: 22+48+8+22+7=107; Dengue Severity Classification sources 1→2; new Morra row); concepts/Dengue Severity Classification.md (+2 Key-Points bullets on within-scheme heterogeneity + the attributed Macedo 73.0%/93.4% line, inserted before ## Contradictions & Debates; +a “two axes that stack” Contradictions note; Morra added to ## Sources); analyses/Notable Findings.md (+1 entry, new top, extending the same-date Narvaez between-scheme entry); curated propagation links into sources/GarciaBates2013 - Plasmablast Response and Dengue Severity.md and sources/GodoyLozano2016 - Lower IgG SHM Rates in Acute Dengue.md (lightweight inline parentheticals, house style — no ⚠ banner). Sub-agents: 3 used — 1 read-only propagation mapper (Explore), 2 parallel page drafters (general-purpose, non-overlapping files: source page vs concept+Notable Findings). Mapper scoped to the sharp question (which pages assume same-scheme comparability that Morra qualifies), returned GarciaBates2013 + GodoyLozano2016 as the top curated targets; Thesis Objectives assessed and deferred as lower-value. Scope discipline: No entity or method pages created — clinical-classification review outside the wiki’s B-cell/flow-cytometry scope; PRISMA method + clinical signs kept as plain text on the source page (mirrors Narvaez2011). Tight propagation per curator’s choice; corpus-wide backlink of the ~35 severity-mentioning pages still deferred to the lint watch item (now also covering Morra2018). Accuracy guard: the “73.0% (2009) vs 93.4% (1997)” specificity figures are attributed to Macedo et al (cited in Morra), a different cohort/gold-standard than Narvaez’s intervention-anchored 78.5% — explicitly fenced as not a contradiction on both the source and concept pages. Morra itself pools no diagnostic accuracy. Citations: Semantic Scholar 50 (influential 1), CrossRef 48 (retrieved 2026-06-29). Notable finding added: Within one WHO scheme, dengue severity signs are defined inconsistently — only 2 of 16 signs reach consensus under WHO-2009; “shock” defined 23 ways; compounds the between-scheme (Narvaez) finding.

[2026-06-29] ingest | Narvaez F 2011 - Evaluating WHO Dengue Severity Classifications

Created (2): sources/Narvaez2011 - Evaluating WHO Dengue Severity Classifications.md (PLoS NTD; landmark WHO-1997 vs WHO-2009 classification evaluation, n=544 pediatric Nicaragua); concepts/Dengue Severity Classification.md (new canonical hub for the severity axis — both WHO schemes defined side by side + the Narvaez evaluation + the cross-scheme comparability caveat). Updated (6): index.md (Sources 20→21, Concepts 7→8, total 103→106 — the +1 beyond the two new pages corrects a pre-existing total-count drift; section counts now sum to the total); analyses/Notable Findings.md (+1 entry: severity associations are scheme-dependent); curated propagation links to analyses/Research Plan - DN B Cell Expansion in Dengue.md, analyses/Thesis Objectives and Grant Pitch.md, and source pages GarciaBates2013, GodoyLozano2016, Ansari2025 (lightweight inline see [[Dengue Severity Classification]] references, each noting the scheme that source actually used). Sub-agents: 3 used — 1 read-only propagation mapper (Explore), 2 parallel page drafters (general-purpose). Mapper caught that GarciaBates2013 uses Brazil’s national DF/DFC criteria (not WHO-1997) and Ansari2025 uses WHO-2009 (not WHO-1997); both drafter attributions were corrected before writing. Scope discipline: No serotype entity pages and no clinical-epi method pages created (out of the wiki’s B-cell/flow scope); clinical methods listed as plain text on the source page. Concept page ## Sources deliberately anchored on Narvaez2011 only — full backlinking of the remaining ~35 severity-mentioning pages deferred to a future lint (logged as a Watch Item). Citations: Semantic Scholar 238 (influential 11), CrossRef 191 (retrieved 2026-06-29). Notable finding added: Severity associations are classification-scheme-dependent — DENV-2→DHF/DSS (p<0.001) under WHO-1997 vanishes under WHO-2009 Severe Dengue (p=0.104) in the same cohort; schemes agree only κ=0.25.

[2026-06-27] page | DN2 Gating Strategy — added canonical start→finish gating tree

Updated: analyses/DN2 Gating Strategy.md — added “Canonical Gating Tree (Start → All Subpopulations)” as the first subsection of Synthesis: a single consolidated hierarchy (singlets → CD19⁺ → PB pulled first → IgD×CD27 quadrant → sM resting/activated split → DN CD21×CD11c 2×2) plus a flat 9-population terminal checklist and the FMO-anchored cuts. Summarizes and links the existing Step 0–6 detail, sM split, and 4-overlap reconciliation — does not duplicate them. Frontmatter updated → 2026-06-27. Reason: Curator asked for the full gating plan, start to all needed sub-populations, in one summary. The page held all the pieces but had no single at-a-glance map; this adds the entry-point overview before the per-step detail.

[2026-06-27] page | Switched Memory B Cell entity created + DN2 Gating Strategy reconciled

Created: wiki/entities/Switched Memory B Cell.md (IgD⁻CD27⁺ GC-derived memory; 11 sources synthesized from existing wiki pages — no new ingest). Anchors the curator’s new flow gate as the germinal-center comparator to DN/DN2. Updated: analyses/DN2 Gating Strategy.md — added “Isolating Switched Memory (sM)” subsection (resting CD21⁺ / activated CD21⁻ split) + a 4-point reconciliation of the expanded full-B-cell gating tree. Inbound [[Switched Memory B Cell]] links added to Memory B Cell, DN2 B Cell, Double-Negative B Cell, CD27, IgD, Scharer2019, Jenks2018. Index Entities 47→48. Reason: Curator is expanding the 11-color panel to isolate switched memory (sM, IgD⁻CD27⁺) as a population of interest. Briefing flagged 4 gating-tree overlaps to reconcile: (1) memory gates not IgD-anchored (mix switched + unswitched), (2) “ABCs” ≡ “DN CD21⁻CD11c⁺” ≡ DN2-phenotype double-label, (3) missing CD21⁻CD11c⁻ (DN3-like) quadrant, (4) CD24 double-duty (transitional exclusion vs memory inclusion).

[2026-06-27] schema-update | Voice (TTS) Mode workflow added to CLAUDE.md

Change: Added a ### Voice (TTS) Mode subsection to CLAUDE.md §Workflows documenting the /tts-on and /tts-off global slash commands, which now couple the shared Kokoro TTS server (127.0.0.1:8880, GPU) lifecycle to the voice mode so it is not resident when unused. Scope: CLAUDE.md §Workflows only (inserted between Update Web and Lint). Entry explicitly marks these as global/infra commands, not wiki operations. Pages affected: none (CLAUDE.md + log + state only). Reason: Curator: server was running constantly; wanted a terminal trigger to start/stop it with the voice mode. Built start_kokoro_detached.ps1 (idempotent detached launch, waits for /health 200) and stop_kokoro.ps1 (kills the 8880 listener), wired into /tts-on (start → set flag, aborts if server fails) and /tts-off (remove flag → stop server). Round-trip tested: stop→health 000, detached start→health 200 in ~2s. Scripts/commands live under ~/.claude/, outside this repo.

[2026-06-26] prep | Pre-meeting reframe — prelim meeting is wiki-first, not pitch-first

Context: Morning-of, in-lab session immediately before the meeting with Prof. Rukie. Curator clarified the framing: this is the preliminary meeting, so Prof. Rukie is most likely interested in the wiki as a tool/method rather than the PhD pitch, and it is the first time the wiki + Claude are being introduced to her. Reoriented the last-minute prep accordingly.

Reframe delivered (no plan file edits — verbal prep only):

One-breath intro: living literature-review knowledge base — 20 papers, 100+ interlinked pages — that Claude maintains (summarize → cross-link cells/markers/methods/concepts → flag contradictions).
Three rigor talking points (lead with these if skeptical): (1) evidence weighting — study type + n inline on every claim; (2) it flags contradictions and downgrades claims (Ansari severity downgrade; Tph-identity doubt) rather than smoothing them; (3) the Council adversarial-review layer (Ansari2025 report on standby).
Demo order by impact: Obsidian graph → one source page (Ansari2025 structure) → live site efb-dengue-wiki.pages.dev.
Introducing Claude: “Claude summarizes/cross-references/maintains; I curate and direct.” Honesty stance is the selling point — if asked “does it hallucinate,” answer plainly: everything traces to a source page, fact-checked pre-meeting (caught the GodoyLozano n=175→19 error yesterday).

No wiki pages modified — prep/consult only. Next sign-in will be live, in front of Prof. Rukie.

[2026-06-25] prep | PhD meeting fact-check pass + corrections + cold rehearsal

Context: Final prep for tomorrow’s (2026-06-26) PhD-upgrade meeting. Fact-checked every spoken number in the meeting plan (~/.claude/plans/pure-zooming-adleman.md) against the wiki sources + the Ansari2025 council report — the tool-pitch rests on “every number traces to a paper,” so a wrong figure in front of these PIs is the highest-cost failure.

Defects found & fixed in the meeting plan:

GodoyLozano2016 cited as n=175 in TWO places (Act 1 narration + the SHM-contradiction Q&A answer) → corrected to n=19 acute patients (“385,206” is the lineage count, not patients). Highest-value catch — a wrong cohort size in front of immunologists who know the paper would undercut the whole traceability pitch.
“99 interconnected pages” → “over 100 … built from 20 papers” (actual: 103 content pages / 106 with infra; live site 118). Robust to whatever’s on screen tomorrow.

Additions to the meeting plan:

O1-is-novel one-liner in Act 1 + mirrored on the Act 4 primary-objective bullet (Ansari correlated Tph with the DN2-phenotype cells; nobody has correlated those cells with antibody quality/ANA — that correlation is O1).
7th expert-question row targeting O1 directly (“your primary endpoint is a ratio of populations you can’t definitively identify”) with a concede-then-redirect answer.
Sharpened the 4 explicit asks into direct spoken questions (+ delivery note: ask as questions, pause on each).

Verified accurate (no change needed): Ansari2025 n=170 (council-confirmed); pilot n=19 (DF=8/DHF=11); Sutton ~45% undercount (44.7% of atBC1, CD11c best single marker); Tph = Th1-signature concern + IL-21 coculture STRONG; severity downgraded for day-of-sampling (8±4 vs 5±2 d). Council report present and on-message.

Cold rehearsal: ran all 7 hard Q&A as spoken answers with second-order follow-ups; flagged Q1 (Tph identity) + Q2 (SHM paradox) as the two that can spiral, with the same safety-pivot for both — don’t defend the weak link, redirect to what the pilot actually measures (cells→ANA).

No wiki pages modified — prep/consult only.

[2026-06-25] ops | PhD upgrade pitch prep — meeting with Prof. Rukie and Prof. Neelika

Context: Osanda is presenting his MSc→PhD upgrade case tomorrow to co-PIs Prof. Rukie and Prof. Neelika. The meeting has two goals: (1) validate the EF/atypical-B-cell direction as scientifically novel and fundable; (2) secure upgrade endorsement pending pilot results.

Plan created: ~/.claude/plans/pure-zooming-adleman.md — full meeting structure including narrative arc, expert Q&A bank, demo moments, and explicit asks.

Key structure:

Act 1 (Osanda): the gap — GodoyLozano2016 low SHM + Ansari2025 cellular phenotype + the unbuilt cells→ANA bridge
Act 2 (Osanda + demo): Obsidian graph + source/entity page walkthrough — every claim is traceable
Act 3 (PIs → Claude cold): expert Q&A; PIs are deep B-cell immunologists; six hard questions pre-prepared (GC/EF balance, CXCR5/T-bet absence, Sutton44.7% undercount, GodoyLozano/Priyamvada SHM contradiction, Tph identity, age confounding)
Act 4 (Osanda): pilot design → PhD trajectory → explicit upgrade ask

Pre-meeting checklist: fresh Claude session pre-loaded with project context; Obsidian graph open; Claude-council/council final report-Ansari2025.md on standby as proof of adversarial review.

Explicit ask to PIs: (1) O1 is a scientifically novel primary objective; (2) d5–8 n≈20 design is appropriate for a pilot; (3) positive pilot justifies a funded mechanism study; (4) support upgrade application.

[2026-06-25] consult | Gating strategy for rN/aN/usM/sM in 11-color panel

Question: What is the best gating strategy for naive B cell subsets (rN = resting naive, aN = activated naive), unswitched memory (usM, IgD⁺CD27⁺), and switched memory (sM, IgD⁻CD27⁺) in the existing panel?

Panel: RB705-CD19 · BV785-IgD · APC-CD27 · FITC-CD21 · PE-CD11c · BV421-CD38 · PE-Cy7-CD66b · eFluor506-L/D · BV711-CD3/CD14 · AF700-CD24 · APC-Fire750-CD45.

Answer summary:

Tier 1 (IgD × CD27 quad): usM = IgD⁺CD27⁺; sM = IgD⁻CD27⁺; total naive parent = IgD⁺CD27⁻. No new gating structure needed — same quad already used for DN.
Tier 2 (within naive — CD21 × CD11c): rN = CD21-high/CD11c⁻ (follicular); aN = CD21-low/neg/CD11c⁺ (pre-ABC, matches the existing aNAV gate). Critical caveat: the FMO-anchored CD21 cut (0.33, arcsinh) was calibrated in the DN context — naive B cells sit dramatically higher on CD21 (follicular phenotype). The rN/aN CD21 boundary must be set visually within the naive gate, not by transferring the DN-context cut. CD11c cut (0.28, FMO p99.5) transfers well.
Panel constraints: CD24 is comp-compromised (large spill from CD3/CD14→CD24 1.44) — cannot use for transitional exclusion. CD38 has batch drift — use per-batch cut for transitional exclusion from usM if needed.
usM transitional contamination: optional exclusion via CD38-bright (per-batch cut required).

Pages not modified — consultation only; no wiki updates triggered.

[2026-06-16] flowjo check | CD66b dump gate vs CD19+ spread (Specimen_001_HT 82_002.fcs)

Purpose: Verify the CD66b-PE-Cy7 dump gate is not excluding B cells from the B cell denominator (the highest-priority pre-cohort QC check).

Method: Built CD19 (PerCP-Cy5-5) vs CD66b (PE-Cy7) 2D plot on the live leukocyte parent population; gated the CD19+CD66b+ region; checked FSC-A vs FSC-H for doublets; checked whether CD66b scales with CD19 brightness (spillover test).

Findings:

Main B cell cluster (CD19~10⁴, CD66b 10¹–10²): clean and well below dump threshold — no B cells lost here
CD19+CD66b+ population: 5,789 events, 1.70% of 336,780 live leukocytes, ~19.5% of current B cell denominator (29,665)
Confirmed singlets — FSC-A vs FSC-H tight diagonal; two prior singlet gates already in hierarchy; doublet hypothesis eliminated
Spillover ruled out — brightest CD19 events (main B cell cluster) are the most CD66b-negative; PerCP-Cy5-5→PE-Cy7 artifact would produce the opposite pattern
These are real CD19+CD66b+ single cells being actively excluded by the dump gate

Decision pending: See Watch Item [2026-06-16]. Options: (a) widen dump boundary to recover them; (b) keep gate, note as formal limitation. If recovered: true B cell N = 35,454; DN% = 7.45% (vs current 8.90%).

Next step (resume point): Decide dump gate strategy, then characterise CD19+CD66b+ events on IgD/CD27/CD21/CD11c to assess whether plasmablast-enriched.

[2026-06-14] new method page | DN2 Panel - Staining, Compensation, and Gating Protocol

What: Created wiki/methods/DN2 Panel - Staining, Compensation, and Gating Protocol.md — an end-to-end operational SOP for the curator’s 11-color DN2 panel, covering fresh whole-blood prep, control-tube construction (unstained, single-stain beads + the cells-based AmCyan/L-D exception, and the four FMOs), acquisition/CST routine, FlowJo compensation, and FMO-anchored gating, with worked examples, analogies, a possible-issues/mitigations table, and an honest “True Protocol Limitations” section.

Scope: This page owns the bench-to-screen procedure; it links to (rather than reproduces) the numeric spillover/FMO tables in Compensation and FMO Controls and the Step 0–6 gating hierarchy in DN2 Gating Strategy. Real fluorochrome names used throughout (APC-H7=CD45, AmCyan=L/D, PerCP-Cy5-5=CD19, BV786=IgD), per the existing naming-drift watch item.

Pages updated: index.md (Methods 21→22, pages 101→102), methods/Compensation and FMO Controls.md (Related Pages link), analyses/DN2 Gating Strategy.md (Related Pages link), state.md.

Session: governed by ~/.claude/plans/we-need-to-check-cosmic-taco.md; advisor consulted twice (plan scope-fencing, then final review).

[2026-06-14] new method page | Compensation and FMO Controls

What: Created wiki/methods/Compensation and FMO Controls.md — general compensation-vs-FMO principles (sourced from Wei2007 - DN Memory B Cells in SLE, Singh2026 - DENV-Specific Memory B Cell Subsets) plus the curator’s empirical worked example from the 11-color DN2 Gating Strategy panel pilot.

Worked example summary: Compensation matrix validated as sound (cond=6.22, det=0.907); the CD21→CD11c spillover (~20%, the DN2-axis pair) confirmed clean. Four FMOs (CD11c-PE, CD21-FITC, CD27-APC, IgD-BV786) showed the working DN cutoffs (IgD<0.8, CD27<1.0) were undercounts relative to FMO-negative 99th percentiles (1.98 / 1.76). Curator adopted the FMO-anchored box (IgD<1.98 & CD27<1.76) as DN, quadrupling DN from 591 (1.99% of B cells) to 2,640 (8.90%); DN2 (CD21<0.69 & CD11c>0.72 within DN) = 211/2,640 = 7.99% of DN.

Pages updated: index.md (Methods 20→21), analyses/DN2 Gating Strategy.md (Related Pages link), state.md (Watch Items — resolved compensation/FMO item, added naming-drift, bead-validation, and CD11c-precision follow-ups).

Session: governed by ~/.claude/plans/we-need-to-check-cosmic-taco.md; full numeric/script trail in Flowdata/STEP5_FINDINGS.md.

[2026-06-14] consult | Compensation & CD11c-FMO cadence (11-color DN2 panel)

Question: Curator asked how to compensate better on the fixed 11-color whole-blood DN2 panel (DN2 Gating Strategy) and whether the CD11c-PE FMO is needed per-sample or “one or two.” Plan-mode consultation; advisor-reviewed; plan approved (~/.claude/plans/memoized-finding-cloud.md).

Setup facts gathered (drive the answer): whole blood + RBC lyse; daily CST standardization; single aliquoted CD66b-PE-Cy7 lot; small cohort (<20, a few staining days); FlowJo v10.

Recommendation (pending empirical validation): per-batch (per-staining-day) CD11c-PE FMO, not per-sample. Rationale: compensation corrects the spillover median, not the spreading that widens the negative (the FMO’s job); the three cadence drivers — PMT drift, lot-to-lot tandem variation, degradation window — are all controlled here; and DN2 cells are CD66b⁻ / CD21-low, i.e. the low-PE-spread corner. Whole-blood risk is granulocyte contamination (a gating-hygiene fix: tight doublet + CD66b/CD45 exclusion), not boundary drift. Pull-back trigger: FMO 99.5th-pct PE boundary drifts >~0.5 log across batches.

Next: interactive FlowJo walkthrough (control inventory → spillover-spreading-matrix PE row → PE-Cy7→PE degradation tail → cross-batch CD11c boundary test) → then write wiki/methods/Compensation and FMO Controls.md (general principles + this panel’s worked example) with standard cross-links + index/log/state updates. No wiki pages created yet — walkthrough pending curator’s FlowJo data.

[2026-06-14] analysis | B Cell Panel Variant 1

Created: wiki/analyses/B Cell Panel Variant 1.md — first design iteration of an intracellular-capable B-cell panel for the curator’s 3-laser (405/488/633), 14-detector conventional cytometer (config supplied this session: no 561/no UV → PE-family forced onto blue laser; 6 BV on violet). Leans toward atypical/DN sub-populations + plasmablasts. Advisor-reviewed once before drafting.

Design spine: intracellular capability adds T-bet (converts “DN2-phenotype” → confirmed DN2/ABC) and the panels add CXCR5 (unlocks the DN2:DN1 ratio centerpiece — impossible on the surface-only DN2 Gating Strategy 11-color). Premium-channel scarcity (only APC + BV421 truly bright/low-spread; PE a crowded third) forces the four dim defining markers (CXCR5/CD11c/T-bet/FCRL5) to compete → FCRL5 yields (corroborating, not defining per Jenks). Three defining axes (CD11c⁺/CXCR5⁻/T-bet⁺) kept on premium channels in every panel.

Curator-directed shape: single tube is the realistic constraint → Panel 4 (13-color single-tube workhorse) is the lead recommendation, with the 14th (PE-Cy7) slot deliberately left empty to eliminate the wiki-flagged PE-Cy7→CD11c-PE false-positive artifact. Panels 1–3 reframed as the multi-tube suite (Panel 1 anchor = +IgM/CD24; Panel 2 = ASC/effector output; Panel 3 = isotype×chemokine). Panel 4 covers both halves of the thesis (DN2 confirmation + DN2:DN1 ratio + plasmablast/EF-effector) in one acquisition.

Honest caveats embedded: 14-color is the feasibility ceiling not a target (clean 13 > saturated 14); fluorophore slots not SKUs (must verify conjugates + run spreading matrix before ordering); fixable L/D + surface-before-fix (CXCR5/CXCR3 at 37 °C) + TF perm + tandem-survival checks; CD11c-PE FMO mandatory; none resolve DENV-antigen specificity (grant-level).

Bookkeeping: index Analyses 6→7, Total pages 100→101. Inbound links added from DN2 Gating Strategy (as successor) and Thesis Objectives and Grant Pitch Related Pages (no orphan). Dropped a dangling [[Ki-67]] link (no entity page exists — Ki-67 referenced inline across wiki but unbuilt; noted as a gap in state). All other wikilinks resolve.

[2026-06-14] analysis | Thesis Objectives and Grant Pitch

Created: wiki/analyses/Thesis Objectives and Grant Pitch.md — strategic/objectives layer for the curator’s dengue atypical-B-cell pilot, complementing the wet-lab [[Research Plan - DN B Cell Expansion in Dengue]] (Rev 4). Built across a multi-turn brainstorm (gating strategies → fixed-panel resolution ceiling → pilot design → grant pitch), advisor-reviewed once mid-session.

Core content: central thesis (one low-fidelity antibody property — cross-reactive/polyreactive/near-germline — with two faces: autoreactivity + non-neutralization/ADE; EF/DN2-phenotype + plasmablast compartment as proposed source, SLE-imported and unproven in dengue); 5 falsifiable objectives with O1 = cells→ANA correlation as the novel primary (continuous, full-cohort); statistical-honesty framing (continuous-correlation-first at n≈10–15/arm; severity as exploratory/effect-size-generating); confounder pre-emption.

Key analytical contributions this session: (1) age & sex are first-order confounders for ABCs (age-defined; female-biased via X-linked TLR7) — current arms imbalanced (DHF male-skewed/older; DF female-skewed/younger) → fix by balanced recruitment now, not adjustment; (2) the d5–8 window is a built-in timing control that de-risks the severity confounder that sank Ansari2025’s severity claim; (3) both faces measurable in-pilot now that ANA + FRNT×4 (all serotypes grown) + IgG/IgM are available; (4) LFA→capture-ELISA κ-validation design for serostatus; (5) WHO-2009-binary-primary + WHO-1997-leak-sensitivity severity recommendation (flagged as curator’s call).

Sample reality captured: 19 cases (DF=8, DHF=11), cross-sectional, d5–8, single serum timepoint; target ≥10–15/arm; recruitment ongoing.

Bookkeeping: index Analyses 5→6, Total pages 99→100; inbound link added from Research Plan Related Pages (no orphan). All wikilinks resolve to existing pages.

[2026-06-14] deep lint | Post-reframe + Lamprinou2026 health check (100 pages, 3 parallel agents)

Scope: Full wiki audit by three parallel read-only sub-agents — sources/ (20), entities/ (47), concepts/+methods/+analyses/ (33). First deep lint since the 2026-06-13 spine reframe and the Lamprinou2026 ingest. Agents ran standard structural checks + reframe-consistency checks (stale “ABC = DN2” flat equivalence; EF-as-organizing-frame framing; DN1–DN3 vs DN1–DN4 nomenclature; new hub-page reciprocity).

Structural health: EXCELLENT. 0 HIGH findings across 100 pages. Zero broken wikilinks, zero orphans, zero displaced content (insertion-order guard holding since 2026-05-08), zero frontmatter source-count mismatches, 100% template compliance. The reframe propagated cleanly — no stale flat ABC=DN2 equivalence found; asymmetric-overlap nuance consistent across hub and sub-pages. Lamprinou2026 ingest verified clean across all touched pages.

Issues found and fixed (8):

Severity	Issue	Fix
MED ×6	Source pages cited as Sources ON the new hub pages but not linking back in their own “Entities Mentioned” (reframe created hubs citing pre-existing sources; reverse link not propagated)	Added `[[Atypical B Cell]]` to Jenks2018, Woodruff2020, Ansari2025, Singh2026; added both `[[Atypical B Cell]]` + `[[Age-Associated B Cell]]` to Sanz2025, Sutton2021
MED ×1	`Extrafollicular Response` Overview still framed EF as “the central biological focus of this wiki” (pre-reframe)	Reworded to position EF as the generating pathway under the atypical (DN) B-cell + plasmablast spine
LOW ×1	`T-bet` Overview leaned toward flat ABC/atypical/DN2 equivalence	Softened to “overlapping (but non-identical) labels” + pointer to Atypical B Cell synonymy map

Curator Highlights refreshed: 2 highlights, both current (Ansari2025 (acute cells died in culture); DN2 Gating Strategy Whether this concordance holds in dengue is unknown.). No content change; updated: bumped to 2026-06-14.

Deferred (already-tracked LOW items, no action): evidence-weight annotations missing on early marker pages (CD19/CD27/CD38/CD10); IgA/IRF4 list a source not cited in any Key Points bullet; External Citation Audit is a 2026-05-08 snapshot now stale vs. 20 sources (Lamprinou2026’s external cites uncatalogued); thin single-source method/entity pages (expected). All remain in state.md Watch Items.

[2026-06-14] ingest | Lamprinou2026 - ABCs and DN B Cells

Source: raw/Lamprinou2026.pdf (DOI: 10.3389/fragi.2026.1752452) → Lamprinou2026 - ABCs and DN B Cells Type: Opinion / narrative conceptual synthesis (Frontiers in Aging); no original data. Taxonomy and several core claims are self-cited to the author group (Sachinidis/Garyfallos); weighted accordingly throughout. Key contribution: First wiki source dedicated to the ABC ↔ DN identity question the Atypical B Cell umbrella was built to map. Establishes ABC as a heterogeneous superset (CD27⁺ + IgD⁺ + predominantly IgD⁻CD27⁻) whose IgD⁻CD27⁻ fraction maps to DN2; CD27⁺/IgD⁺ ABCs and the CXCR5⁺/T-bet⁻ DN subsets fall outside the overlap, which is partial and context-dependent. Even within the shared T-bet⁺CD11c⁺ phenotype, ABCs are transcriptomically distinct from DN2 (Maul 2021). Mechanistic refinement: IL-21 → CD11c, IFN-γ → T-bet in the TLR7/9-driven ABC differentiation programme. Introduces a four-subset DN taxonomy (adds DN4: CXCR5⁺CD11c⁻T-bet⁻, allergy-associated) vs. the wiki’s default three (DN1/DN2/DN3) — logged as nomenclature drift, not a contradiction. No dengue data. Pages created: 2 (source page; entities/Age-Associated B Cell.md — new) Pages updated: 20 (15 entities: Atypical B Cell, Double-Negative B Cell, DN2 B Cell, DN3 B Cell, T-bet, CD11c, CXCR5, CD27, IgD, IgG, IgA, TLR7, IL-21, CD20 + Age-Associated B Cell [new]; 4 concepts: Extrafollicular Response, Germinal Center, Somatic Hypermutation, Class Switch Recombination; index) Notable Finding: “ABC” is a superset that only partly overlaps “DN” — and is transcriptomically distinct from DN2 even where they overlap (entry #16). Qualifies the post-reframe “ABC ≈ DN2” shorthand on the Atypical B Cell umbrella. Citations: Semantic Scholar 1, CrossRef 1 (retrieved 2026-06-14 — null on first attempt 2026-06-13, paper too new to be indexed). Note: Ingest began 2026-06-13 and was interrupted before the closing steps (citations retry, log, state.md, commit); resumed and completed 2026-06-14. Propagation verified clean across all 19 updated pages (insertion-order guard held).

[2026-06-13] reframe | Atypical B Cell umbrella + spine reframe (complete)

Change: Executed the spine reframe toward atypical/age-associated B cells + plasmablasts (per CLAUDE_GOVERNANCE pre-change checklist; pre-reframe git snapshot 8471e8c). Created the [[Atypical B Cell]] umbrella/hub entity page — a synonymy map (atypical/ABC/T-bet⁺/CD11c⁺/DN/alternative-lineage → precise sub-populations) that foregrounds the Sanz2025 “atypical is misleading” debate and routes to Double-Negative B Cell, DN2 B Cell, DN3 B Cell, Activated Naive B Cell without restating their content. Reframed the Double-Negative B Cell page to defer to the umbrella (resolves the “two primary-home pages” ambiguity). Conflict resolved: Supersedes the [2026-05-02] decision against splitting atypical/ABC out of Double-Negative B Cell (curator-sanctioned via the greenlit watch item). DN nomenclature remains the precise classification; “atypical” is the field-level umbrella only. Pages affected: 3 — created entities/Atypical B Cell.md; updated entities/Double-Negative B Cell.md, index.md, state.md. CLAUDE.md identity — APPLIED (hybrid “Atypical (DN)” term, curator’s choice): Rewrote CLAUDE.md H1 (→ “Atypical (DN) B Cells & Plasmablasts in Dengue”), mission, and Domain Context intro to lead with “atypical B cells (the DN / age-associated cluster, IgD⁻CD27⁻) and plasmablasts,” with EF reframed as the generating pathway and the flow-cytometry methodological focus retained. Minimal diffs per CLAUDE_GOVERNANCE; no other CLAUDE.md sections touched. Rollback point: snapshot 8471e8c.

[2026-06-13] direction | New high-level direction + bridge-wiki created

Change: Curator set a new high-level research direction — “plasmablasts and atypical/age-associated B cells and their association with autoantibodies and neutralizing antibodies in dengue.” Scope brainstormed with advisor review. Resolved into a three-wiki architecture: dengue-wiki/ (antibodies/ANA/autoimmunity — canonical; ~45 sources), efb-dengue-wiki/ (this — cells/EF/atypical B cells/plasmablasts/flow — canonical), and a new bridge-wiki/ (synthesis layer connecting cells→autoantibodies).

Central thesis: the atypical/plasmablast compartment produces one low-fidelity antibody property (cross-reactive, polyreactive, near-germline) with two clinical faces — autoreactivity (molecular mimicry) and non-neutralization/ADE; anti-NS1 and anti-prM are the linchpin specificities. The novel/unbuilt arm is cells→autoantibodies; neut/ADE/OAS is already double-covered in both parents (reconcile, not build).

Created: bridge-wiki/ (sibling folder under Literature Review Dengue/) — seam option (c): standalone bridge artifact with its own CLAUDE.md, state.md, log.md, index.md, and seed synthesis syntheses/Atypical B Cells to Autoantibodies - Bridge Thesis.md. No merge of the parent wikis (both exceed comfortable session-context limits). Memory updated (three-wiki-architecture, lean-structures-context-limits).

Pages affected (efb-wiki): 0 wiki pages modified. state.md updated (Current Focus direction note, Decisions entry, 3 Watch Items for proposed efb changes).

Proposed (NOT done — need curator go-ahead): (1) split out an [[Atypical B Cell]] umbrella page (reopens [2026-05-02] fold-into-DN decision); (2) reframe efb spine from “extrafollicular response” to atypical B cells + plasmablasts, EF demoted to a pathway.

[2026-05-24] revision | Research Plan - DN B Cell Expansion in Dengue → Revision 4

Change: Major update to the Research Plan analysis page. Systematic “DN2” → “DN2-phenotype” / “DN1” → “DN1-like” / “DN3” → “DN3-like” terminology correction throughout (per Sanz2025/DN2 Gating Strategy — panel lacks CXCR5/T-bet/FCRL5). Three new Background subsections: tissue-level GC loss (Kaneko2020), EF SHM precedent (William2002), alternative lineage framework caveat (Sutton2021). H4 softened from strict precursor–product to co-variation model (informed by Sutton2021 no-PC-genes finding). Two new limitations (Sutton2021 44.7% gating capture; Bhattacharya2016 tissue-retained PBs). Gating strategy cross-referenced to DN2 Gating Strategy analysis; council-identified warnings integrated. New Follow-Up Study 8 (CD11c-primary gating reanalysis). Sources Used expanded by 7 references. Related Pages expanded with new entities (TNF-alpha, Bcl-6, AID, FCRL5, IgM), methods (CITE-seq, scRNA-seq), and all new source pages. Pages affected: 1 (wiki/analyses/Research Plan - DN B Cell Expansion in Dengue.md) Sources integrated: Kaneko2020, William2002, Sutton2021, Bhattacharya2016, Priyamvada2016, Singh2026, GarciaBates2013

[2026-05-24] schema-update | CLAUDE.md refactor — lazy-load council, rename governance, trim fat

Change: Three-part schema refactor to reduce per-session token load: (1) Council workflow extracted from CLAUDE.md to lazy-loaded CLAUDE_COUNCIL.md; (2) CLAUDE_UPDATE.md renamed to CLAUDE_GOVERNANCE.md with baseline improvements table removed; (3) New Axis / Remove Axis stubs in CLAUDE.md replaced with pointer to governance file. Scope: CLAUDE.md §Architecture, §Workflows (Summon the Council, New Axis, Remove/Merge Axis); CLAUDE_GOVERNANCE.md (renamed, trimmed); CLAUDE_COUNCIL.md (new file) Pages affected: 0 (schema-only change; no wiki pages modified) Reason: Curator-directed refactor to improve per-session token efficiency. Council protocol (~2,300 tokens) loaded every session but used ~1 in 10. Axis stubs duplicated governance file content. Baseline table was historical, not operational. Net savings: ~2,400 tokens removed from per-session CLAUDE.md context load (~115 lines).

Baseline Improvements table (moved here for historical record):

The following changes were identified as structural deficiencies in the original instruction set and incorporated into CLAUDE.md as defaults. Previously tracked in CLAUDE_UPDATE.md (now CLAUDE_GOVERNANCE.md); moved here 2026-05-24 as the changes are applied and no longer need governance-file prominence.

Change	Rationale	Applied to
Context-scaling note in Lint	Wiki growth will exceed single-context scan capacity	§ Lint
Git snapshot step in Ingest and governance	No rollback without version history	§ Ingest + governance file
Citation count usage guidance	Raw counts mislead without age/field context	§ Conventions → Frontmatter
Evidence-weighting on concept pages	All sources weighted equally by default; RCTs ≠ case reports	§ Conventions → Concept pages
”Questions Raised” → Watch Item propagation	Questions were being written but never acted on	§ Ingest step 12
Minimal analyses/ template	Analyses folder had no structure; heterogeneous content	§ Conventions
Retraction/correction workflow	No mechanism to handle superseded papers	§ Workflows
Notable Findings bootstrapping note	Early wiki has a low bar problem	§ Notable Findings
Fast-track ingest flag	Bulk ingests stalled on mandatory discussion step	§ Ingest

[2026-05-23] thicken | OAS and ADE concept pages — Category 5 thin page resolution

Scope: Both pages expanded from 2 sources each to 7 (OAS) and 5 (ADE). Deep lint Category 5 resolved. OAS (Original Antigenic Sin): Added 5 Key Points bullets (GodoyLozano2016 lower SHM, Parameswaran2013 convergent CDR3s, Appanna2016 selective E-specific recruitment, Bhattacharya2016 isotype-fate segregation, Ansari2025 Tph recall engine). Added 1 Contradiction (GarciaBates2013 infecting-serotype dominance as counter-evidence). Page reframed from “OAS in dengue” to “OAS in dengue is contested/conditional.” ADE (Antibody-Dependent Enhancement): Added 4 Key Points bullets (GarciaBates2013 PRNT₅₀ disconnect, Ansari2025 nAb paradox replication, Woodruff2020 cross-disease nAb paradox, Bhattacharya2016 PB insufficiency). Updated Contradictions to note nAb paradox as cross-disease pattern with explicit gap: no study has assayed ADE activity of EF-phenotype-derived antibodies. Source page back-links added: GarciaBates2013 (→OAS, ADE), GodoyLozano2016 (→OAS), Appanna2016 (→OAS), Ansari2025 (→OAS, ADE), Woodruff2020 (→ADE). Pages edited: 9 (2 concept, 5 source, index, log).

[2026-05-23] deep-lint-fix | Concepts folder — 4 categories, 24 fixes applied

Scope: All 7 concept pages audited by 4 parallel sub-agents (structural, bidirectional links, content quality, council cross-check). Full report in tempstate-lint.md. Categories fixed:

Category 1 (Mechanical): Cross-links added to OAS (→GC, CSR), ADE (→GC, SHM), CSR (→MBC, OAS). Evidence weight annotations added to OAS (1 bullet) and ADE (2 bullets). Anolik2004 added to SHM/CSR sources with frontmatter count updates.
Category 2 (Propagation): GC page CXCL13 hedging propagated from EF page (HIGH — was a direct contradiction). SHM/CSR Woodruff2020 n=1 caveats added. SHM dual-pathway labeled “working hypothesis”. CSR Contradictions & Debates populated (was empty).
Category 3 (Content rewordings): 3 HIGH + 7 MEDIUM applied to EF Response page. Key changes: Woodruff n=1 scVDJ “confirms”→“consistent with”; nAb paradox “establishes”→“suggests” + n=3-4 caveat; self-limited autoreactivity generalizability caveat; Tph sampling confounder noted; Th1 signature mismatch noted; Jenks2018 “mapped”→“proposed”; TRAF5 “explains”→“correlates with”; SLE comparison “nearly indistinguishable”→“phenotypically similar”; alternative lineage presence ≠ non-pathological function; coculture memory T cell caveat added to EF + MBC pages.
Category 4 (Verification): Wrammert2012 GC link confirmed (implied, no bullet needed). Anolik2004 added to SHM/CSR. Priyamvada2016→GC bidirectional link fixed. Pages edited: Germinal Center, Somatic Hypermutation, Class Switch Recombination, Original Antigenic Sin, Antibody-Dependent Enhancement, Extrafollicular Response, Memory B Cell, Priyamvada2016 source page. Deferred: Category 5 (thin page thickening for OAS/ADE) — curator-directed. Item #27 (8 content coverage gaps) — needs source-page verification. Item #28 (EF Dengue Context non-standard section) — intentional.

[2026-05-22] ingest | Kaneko2020 - GC Loss and TFH Block in COVID-19

Source: raw/Kaneko2020.pdf (DOI: 10.1016/j.cell.2020.08.025) Key contribution: Post-mortem tissue (LN/spleen, n=11 COVID + controls) + peripheral blood (n=68) analysis demonstrating complete GC absence in COVID-19. Bcl-6⁺ GC B cells and Bcl-6⁺ GC-TFH absent despite AID⁺ B cell preservation — establishing that SHM/CSR enzymatic machinery operates at EF sites. TNF-α accumulation proposed as the mechanism blocking TFH differentiation. TH1 (T-bet⁺) CD4⁺ expansion in tissue. FDC network intact. 13-color B cell panel (BD Symphony) confirms DN, aN, PB expansion; dual-fluorophore probes demonstrate SARS-CoV-2 RBD specificity in aN, DN2, DN3, and PB populations. This is the tissue-level histopathological foundation for the EF dominance model in acute viral infection. Pages created: 6 (source page, Bcl-6, AID, TNF-alpha, ICOS, Multi-color Immunofluorescence) Pages updated: 23 (10 with substantive Key Points: Germinal Center, Extrafollicular Response, Double-Negative B Cell, DN2 B Cell, DN3 B Cell, Plasmablast, Activated Naive B Cell, T-bet, CXCR5, Notable Findings; 11 source-line-only entities: CD19, CD27, IgD, IgG, CD38, CD21, CD11c, CD138, CD10, Somatic Hypermutation, Class Switch Recombination; 2 method source-line-only: Conventional Flow Cytometry, FACS Sorting) Notable Finding: AID preserved without Bcl-6 — enzymatic machinery for antibody diversification operates outside GCs in fatal COVID-19 (entry #15) Citations: Semantic Scholar 649, CrossRef 662 (retrieved 2026-05-22)

[2026-05-22] deep lint | Health check (90 pages, 18 sources)

Scope: Full wiki audit — parallel sub-agents scanned sources/ (18 files), entities/ + concepts/ (48 files), methods/ + analyses/ (24 files), plus log.md and state.md.

Findings:

Sources (18): All clean. Full frontmatter, template compliance, cross-references intact. Minor notes: Singh2026 DOI format atypical (bioRxiv); Ansari2025 has inline council caveats (intentional, not a compliance issue).
Entities + Concepts (48): All structurally sound. No content displacement (insertion-order guard holding since 2026-05-08 fix). No source count mismatches. No broken wikilinks. No orphans.
Methods + Analyses (24): All clean. Source counts accurate. Template compliance complete.
Thin pages (sources ≤ 1): 8 entities (B220, CD23, CD71, ATF3, EGR, HOPX, Peripheral Helper T Cell, TOX2) + 9 methods (Spectral FCM, PRNT, Serum Proteomics, Phospho-Flow, AIM Assay, scRNA-seq, T-B Coculture, IHC, RRBS, CITE-seq) — all previously tracked; will thicken with future ingests.
Evidence weight annotations: ~20 Key Points bullets across early-ingested entity pages (Wei2007/Tipton2015 era) still lack inline n= and study type. Previously tracked watch item.
Curator Highlights refreshed: 2 highlights (up from 1) — new highlight in DN2 Gating Strategy added to snapshot.

No new structural defects found. Wiki is in excellent health.

[2026-05-22] ingest | Sutton2021 - Alternative Lineage B Cells in Vaccination and Infection

Source: raw/Sutton2021.pdf (DOI: 10.1016/j.celrep.2020.108684) Key contribution: scRNA-seq (Smart-seq2 + 10x Chromium) + CITE-seq defines “alternative lineage” (atBC1-3 + MBC1) vs “classical lineage” in malaria-exposed and healthy donors. T-bet/CD11c/FCRL5 as defining markers. CD21⁻CD27⁻ gating captures only 44.7% of transcriptomic atBCs — CD11c is the best single marker. ~20% of B cells in healthy donors belong to alternative lineage. No PC maintenance genes in atBCs — challenges EF pre-PB model (context-dependent reconciliation with Jenks2018). MBC1 = quiescent alternative memory (confirms Sanz2025/Faliti2024 prediction). IgG3 enriched in alternative lineage. Vaccination primes alternative lineage. Pages created: 2 (source page, CITE-seq method page) Pages updated: 21 (12 entities: Double-Negative B Cell, DN2 B Cell, CD11c, CD21, CD27, CXCR3, FCRL5, T-bet, IgG, Plasmablast, IRF4, BLIMP-1; 4 concepts: Extrafollicular Response, Memory B Cell, Germinal Center, Somatic Hypermutation; 5 methods: Single-Cell RNA Sequencing, Conventional Flow Cytometry, FACS Sorting, BCR Sequencing + CITE-seq [new]) Notable Finding: Alternative lineage abundant (~20%) in healthy donors and missed by CD21⁻CD27⁻ gating (entry #14) Citations: Semantic Scholar 186, CrossRef 228 (retrieved 2026-05-21)

[2026-05-20] analysis | DN2 Gating Strategy

Type: Council-reviewed analysis — gating strategy design for DN/DN2-phenotype isolation from dengue PBMCs. Panel: 11-color fixed panel (CD19, CD66b, CD11c, CD21, CD38, L/D, CD3+CD14, IgD, CD27, CD24, CD45). Council: 4-member review (Methodology Critic, Claims Validator, Contextual Critic, Strengths Advocate). Strategy endorsed with 4 modifications (generous FSC/SSC, polygon gates, CD11c FMO mandatory, “DN2-phenotype” terminology). Pages created: 1 analysis page (DN2 Gating Strategy.md) + 2 council files Key outcome: 6-step hierarchy replicating Ansari2025 core gates. Passes Sanz2025 IgD audit. Direct comparability to the only dengue DN2 dataset. Three MAJOR technical concerns documented (PE-Cy7→PE spread, CD27 shedding, CD38 compression).

[2026-05-19] ingest | Bhattacharya2016 - Memory B Cell Subset Selection in Secondary Dengue

Type: Commentary / Editorial (EBioMedicine, companion to Appanna2016) Key contribution: Isotype-fate segregation model (Seifert 2015): IgM⁺ MBCs → GC re-initiation, IgG⁺ MBCs → PB differentiation. PB analysis alone insufficient as correlate of long-term DENV immunity. Pages created: 1 (source page) Pages updated: 7 (Memory B Cell, Plasmablast, IgG, IgM, Germinal Center, Original Antigenic Sin, Antibody-Dependent Enhancement) + index Notable findings: None (commentary with no original data) Citations: Semantic Scholar: 1, CrossRef: 1 (retrieved 2026-05-19)

[2026-05-19] deep lint | Health Check

Scope: All 86 pages scanned (16 sources, 41 entities, 7 concepts, 18 methods, 4 analyses). Parallel sub-agents + direct structural checks.

Structural health: EXCELLENT

Frontmatter source counts: 0 mismatches (all match body source lists)
Required sections: 0 missing across all pages
Section ordering: 0 insertion-order defects (no displaced content after Related Pages/Sources)
Broken wikilinks: 0 in wiki pages (4 shorthand-only in log.md — cosmetic)
Orphan pages: 0
Wikilink validity: 100% — all targets resolve to existing files
William2002 propagation: verified complete (all 8 linked pages updated)

Known issues confirmed (no change from prior lint):

Thin entity pages (1 source): ATF3, B220, CD23, CD71, EGR, HOPX, Peripheral Helper T Cell, TOX2 (8 pages)
Thin method pages (1 source): Spectral Flow Cytometry, PRNT, Serum Proteomics, Phospho-Flow Cytometry, RRBS, Activation-Induced Marker Assay, Single-Cell RNA Sequencing, T-B Coculture Assay, Immunohistochemistry (9 pages)
Thin concept pages (1 source): Original Antigenic Sin, Antibody-Dependent Enhancement (2 pages)
Evidence weight annotations: ~15 Key Points bullets across Wei2007/Tipton2015-era entity pages still lack study type/sample size annotations (CD19, CD27, CD38, CD10, IgD, IgA, B220, CD24)
External Citation Audit: 54 external papers catalogued, pending curator review
CD24 lists Scharer2019 in Sources with no Key Points content

New finding:

William2002 Notable Findings entry: absent. The ingest was the foundational EF SHM paper (585 citations, Science) but its finding was already well-known to the wiki via bare citations. Debatable whether a Notable Findings entry is warranted given the finding was not new to the wiki, only newly sourced. Left as curator decision.

Curator Highlights refreshed: 1 highlight (unchanged — ==(acute cells died in culture)== in Ansari2025).

[2026-05-18] ingest | William2002 - Extrafollicular Somatic Hypermutation in Autoimmune Mice

LANDMARK INGEST — first direct demonstration that somatic hypermutation occurs outside germinal centres; foundational murine evidence for the entire EF pathway framework.

Source: raw/william2002.pdf (DOI: 10.1126/science.1073924)

Pages created (2):

sources/William2002 - Extrafollicular Somatic Hypermutation in Autoimmune Mice.md — MRL/lpr lupus-prone mice; RF B cells at T zone–red pulp border; SHM at ~0.3 mut/gene/gen; genealogical trees; FDC-absent, CD11c⁺ DC-rich EF niche; TLR9 co-stimulation; tolerance escape
methods/Immunohistochemistry.md (new: tissue-based protein localisation; multi-colour IHC for EF B cell localisation)

Pages updated (6):

concepts/Extrafollicular Response.md (MAJOR: first direct EF SHM proof; tolerance escape mechanism; TLR co-stimulation as unifying feature; external citation converted to wikilink; sources 15→16)
concepts/Somatic Hypermutation.md (MAJOR: EF SHM at GC-comparable rates; external citation converted to wikilink; sources 14→15)
concepts/Germinal Center.md (GCs not required for SHM; external citation converted to wikilink; sources 14→15)
entities/CD11c.md (CD11c⁺ DCs at EF sites; murine precedent for DC-B cell interaction; sources 5→6)
entities/TLR7.md (TLR9 as mechanistic precedent for TLR-driven EF SHM; sources 3→4)
methods/BCR Sequencing.md (microdissection + Vκ PCR genealogical trees; sources 8→9)

External citations resolved (3): Converted “William et al. 2002, Science” bare citations to proper [[William2002 - ...]] wikilinks on Extrafollicular Response, Somatic Hypermutation, and Germinal Center concept pages.

Citations: Semantic Scholar 585, CrossRef 448 (retrieved 2026-05-18)

[2026-05-18] council-directed edits | wiki/concepts/Extrafollicular Response.md

Based on: Council final report (2026-05-17)

Fixes applied:

[STRUCTURAL] Moved 5 displaced bullets (Singh2026 ×2, Appanna2016 ×1, GarciaBates2013 ×2) from Contradictions & Debates to Dengue Context
[FATAL FLAW] “resolves the SHM paradox” → “offers a plausible reconciliation of” + added hypothesis caveat
[MAJOR] Added Tph-dependent vs. TLR7-autonomous mechanistic divergence note to Dengue Context
[MAJOR] Added BCR-independent DN2→PC generation (Jenks2018) to Key Points
[MAJOR] Added memory DN2 cells (Sanz2025/Faliti2024) to Dengue Context
[MAJOR] Fixed CXCL13 claim — no longer presented as GC biomarker; Tph-derived CXCL13 acknowledged
[MAJOR] Softened Ansari2025 “establishes dominant” → “identifies a major”
[MAJOR] Fixed Jenks2018 IgG claim — removed unverifiable “higher per-cell IgG” claim, replaced with verified ELISPOT data
[STRUCTURAL] Added CXCR3 to Related Pages
[STRUCTURAL] Added memory vs. naive precursor contrast as named Contradictions & Debates entry
[VERIFIED] GodoyLozano2016 “385,206 lineages” confirmed against original PDF (page 6: “reconstructed 385,206 heavy chain lineages derived from 146,565 heavy chain clonotypes”) — also added to source page

Also updated: wiki/sources/GodoyLozano2016 - Lower IgG SHM Rates in Acute Dengue.md (added dataset scale bullet with verified lineage count)

[2026-05-17] lint + council review | wiki/concepts/Extrafollicular Response.md

Council composition: Custom 4-member panel — Accuracy Auditor, Claims Validator, Contextual Critic, Structural Auditor

Verdict: The wiki’s best-populated concept page with strong numerical fidelity (10/12 verifiable claims accurate). Carries one fatal claim error, four major concerns, two structural defects from displaced bullets, two unverified numerical claims, and two mechanistic gaps.

Key findings:

[FATAL FLAW] “This resolves the SHM paradox” — dual-pathway model is a working hypothesis, not a resolution; n=4 + n=19, non-overlapping studies
[STRUCTURAL DEFECT] 5 positive-finding bullets displaced from Dengue Context into Contradictions & Debates (Singh2026 ×2, Appanna2016 ×1, GarciaBates2013 ×2) — end-of-file insertion recurrence
[MAJOR CONCERN] Dengue EF pathway (Tph-dependent, IL-21-mediated) framed as analogous to SLE TLR7-autonomous B cell activation — divergence nowhere flagged
[MAJOR CONCERN] BCR-independent DN2→PC generation absent from page (present on DN2 B Cell and Plasmablast pages)
[MAJOR CONCERN] Memory DN2 cells (Sanz2025/Faliti2024) absent — page frames EF output as exclusively short-lived
[MAJOR CONCERN] GodoyLozano2016 “385,206 lineages” not in source page — unverifiable
[MAJOR CONCERN] Jenks2018 “IgG at higher per-cell levels than DN1 or SWM” not in source page; source page states surface IgG 50% lower on DN2

Output: Claude-council/raw thinking minutes-ExtrafollicularResponse.md, Claude-council/council final report-ExtrafollicularResponse.md

[2026-05-15] council review | Jenks2018 - DN2 B Cells and EF Pathway in SLE

Council composition: Default 4-member panel (Methodology Critic, Claims Validator, Contextual Critic, Strengths Advocate)

Verdict: Genuinely important paper — most rigorous available DN2 definition and EF pathway model (~900 citations). Two STRONG claims (DN2 distinctness, pre-PC identity) supported by convergent multi-omic evidence. Five MODERATE claims: developmental pathway (in vitro only, no lineage tracing), TLR7/TRAF5 mechanism (correlational, no rescue), clinical associations (confounding not disentangled), DN1/DN2 separation (inferred), EF prominence in SLE (peripheral blood only).

Key concerns: (1) RNA-seq/ATAC-seq underpowered (n=3+3); (2) in vitro differentiation system supraphysiological (R848+IFN-γ+IL-21 at pharmacological doses); (3) naive-origin model non-transferable to secondary dengue (conflicts with Ansari2025 memory-dominated pathway and Priyamvada2016 high-SHM PBs).

Cross-member insight: BCR-independent DN2→PC differentiation (Figure 7F) provides a mechanistic explanation for non-DENV-specific bystander plasmablasts in the dengue PB wave — not currently documented in any wiki page.

Output: Claude-council/raw thinking minutes-Jenks2018.md, Claude-council/council final report-Jenks2018.md

[2026-05-15] council review | Sanz2025 - Human Atypical B Cells Overview

Council composition: Default 4-member panel (Methodology Critic, Claims Validator, Contextual Critic, Strengths Advocate) Verdict: Valuable reference-class review from DN2 defining lab; functions as position paper. Central thesis (abandon AtB for DN) rated WEAK evidence — conceptual argument, not experimental validation. Key new concept: memory DN2 cells (>1 year persistence post-vaccination). Dengue literature entirely absent from cross-disease synthesis. Three new watch items added: memory DN2 in dengue, context-dependence for Ansari2025 secondary cohort, DN classification validation status. Output: Claude-council/raw thinking minutes-Sanz2025.md, Claude-council/council final report-Sanz2025.md

[2026-05-15] council review | Woodruff2020 - EF B Cell Responses in COVID-19

Protocol: Full 4-member council (Methodology Critic, Claims Validator, Contextual Critic, Strengths Advocate) dispatched in parallel. PDF read directly from raw/Woodruff2020.pdf. Wiki source page, Extrafollicular Response concept page, and Double-Negative B Cell entity page provided as context to Contextual Critic.

Verdict: Conceptually important paper — first EF pathway demonstration in acute viral infection. Flow cytometry phenotyping (24-marker spectral panel) is the durable contribution. Strongest claims (EF origin of ASC repertoire, SLE equivalence, neutralizing Ab paradox) rest on underpowered data (n=1 scVDJ, n=7 SLE, n=3-4 FRNT).

Claim ratings: 5 claims assessed — 2 MODERATE (phenotypic EF activation, severity correlation), 3 WEAK (neutralizing Ab paradox, ASC repertoire EF origin, DN3 as novel EF population).

Key concerns: n=1 scVDJ (FATAL for repertoire claim), demographic confounding (MAJOR), underpowered FRNT (MAJOR).

Wiki maintenance items identified: (1) CXCR3 entity page should note pre-PB vs. mature ASC distinction; (2) naive vs. memory EF precursor gap between COVID-19 and dengue should be explicitly flagged. Both added to state.md Watch Items.

Output: Claude-council/raw thinking minutes-Woodruff2020.md, Claude-council/council final report-Woodruff2020.md

[2026-05-14] deep lint | Council-augmented deep lint (8 parallel agents + advisor)

Protocol: Three-phase audit combining structural lint (3 parallel sub-agents by folder batch) + council-style specialist review (5 parallel agents: Epistemic Quality, Cross-Reference & Synthesis, Completeness & Gap, Consistency & Style, Reviewer 2) + advisor meta-review. All 8 agents dispatched in parallel. Advisor consulted before applying fixes.

Scope: Full wiki — 84 pages (15 sources, 41 entities, 7 concepts, 17 methods, 4 analyses).

Issues found and fixed (7):

Category	Issue	Fix
Broken wikilinks	5 piped wikilinks in Ansari2025 source page used invented short titles instead of actual filenames (Jenks2018 ×2, Woodruff2020 ×3, Singh2026 ×1, GodoyLozano2016 ×1, Priyamvada2016 ×1)	Corrected all to actual page names
Structural	CXCR3.md had duplicate `## Contradictions & Debates` sections; dengue PB bullet misplaced in first C&D section	Merged sections; moved dengue PB bullet to Key Points
Factual	HOPX.md stated “n=4 patients” for Ansari2025 scRNA-seq; correct count is n=3	Corrected to n=3
Frontmatter	Notable Findings.md `updated:` field had parenthetical annotation `(Priyamvada2016 ingest)`	Removed parenthetical; bare date only
Watch items	state.md: “Dengue plasmablast kinetics benchmark” open (line 94) duplicated by resolved entry (line 147)	Removed open duplicate
Watch items	state.md: SHM resolved item (line 98) duplicated by more detailed resolved item (line 165)	Removed older duplicate
Index	index.md “Last updated” date was 2026-05-10	Updated to 2026-05-14

Curator Highlights refreshed: 1 highlight found — ==(acute cells died in culture)== in Ansari2025 source page. Index updated from “(empty)” to “(1 highlight)“.

Flagged for curator review (not auto-fixed):

Dual-pathway model framing. Multiple agents flagged “resolves” language as overclaiming — the dual-pathway model (memory-derived high-SHM + de novo EF low-SHM) is a working hypothesis, not a resolution. Consider softening to “working hypothesis” across EF Response, SHM, and state.md.
“DN2” vs. “DN2-phenotype” terminology. Ansari2025 shows CD21⁻CD11c⁺ but lacks T-bet/CXCR5/FCRL5 — formally “DN2-phenotype” not confirmed DN2. A systematic rewrite of entity/concept pages to use “DN2-phenotype” where only Ansari2025 is the dengue source would improve epistemic precision.
CXCL13 is not GC-specific. Wiki pages referencing “concurrent EF+GC” based on Ansari2025 CXCL13 data should soften to “suggested by” rather than “demonstrated by.” CXCL13 can originate from Tph themselves.
Tph identity caveat. The CXCR5⁻PD-1⁺ cells in dengue have Th1 signatures (CXCR3⁺, T-bet, IFN-γ), not canonical Tph (MAF⁺, CXCL13⁺ per Rao2017). Consider noting this tension on the Peripheral Helper T Cell entity page.
OAS/ADE page thickening. Both concept pages are single-source (Priyamvada2016). Existing wiki sources (GarciaBates2013 for ADE context, Woodruff2020 for neutralizing Ab paradox) could thicken them.
IFN-gamma entity page missing. Referenced across multiple pages (T-bet signalling, CXCR3 induction, Tph cytokine) but has no entity page.
Evidence weight annotations. ~33% of Key Points bullets across early-ingested pages lack study type and sample size annotations. Concentrated in Wei2007/Tipton2015-era pages.
Missing cross-folder links. Method pages rarely link to concept pages and vice versa (e.g., BCR Sequencing ↛ Somatic Hypermutation).

Reviewer 2 (Devil’s Advocate) top critiques:

FATAL FLAW: The entire EF-in-dengue narrative rests on a single paper (Ansari2025) that lacks T-bet, BCR sequencing, and tissue confirmation. One paper ≠ a paradigm.
MAJOR CONCERN: Cross-disease extrapolation from SLE/COVID-19 is treated as transferable when it should be treated as hypothesis-generating. Different diseases, different immunological contexts.
MAJOR CONCERN: The dual-pathway model is presented as resolution when it’s two datasets that happen to give different numbers — no study has tested both simultaneously.
MINOR NITPICK: The Research Plan assumes DN2 will be found in dengue based on one paper’s CD21⁻CD11c⁺ data without formal DN2 confirmation.

Recommendations:

Next ingest priority: papers with T-bet staining in dengue B cells (confirms/denies DN2), or longitudinal BCR sequencing resolving the SHM paradox.
Consider creating IFN-gamma entity page (referenced in 5+ pages).
Queue papers: balakrishnan2011, kwissa2014 may provide additional plasmablast kinetics and severity data to thicken thin pages.

[2026-05-14] ops | Web deployment updated — council folder added to sync

Action: Updated efbwebshare/sync-and-build.ps1 to sync Claude-council/ into content/council/ (nested under wiki content). Rebuilt and pushed — 89 files processed (2 new council report pages). Cloudflare auto-redeploys.

[2026-05-14] ops | Cloudflare Pages reconnect and redeploy

Action: Cloudflare Pages had disconnected from the Git account, blocking deployments. Curator reconnected in the Cloudflare dashboard. Ran sync-and-build.ps1 — build succeeded (87 files). Initial push rejected (remote ahead); pulled remote changes (Dependabot updates to package.json/package-lock.json). Pushed empty commit to trigger redeploy. Site confirmed live.

[2026-05-14] council-update | Ansari2025 source page updated from council findings

Action: Updated wiki/sources/Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue.md with corrections and nuances from the PDF-based council review. Key changes: (1) scRNA-seq patient count corrected to 3; (2) activated gate clarified as ICOS⁺Ki67⁺; (3) Tph identity tension noted (Th1 signature, not canonical Tph); (4) coculture T cell source specified (seropositive donor memory); (5) day-of-sampling confounder added; (6) CXCL13 non-specificity noted; (7) Tfh coculture comparison documented (Figure 6H exists; blocking Figure 6J is Tph-only); (8) HD sex imbalance, serotype undocumented, FRNT DENV-2-only noted; (9) “first direct evidence” softened to “first phenotypic evidence consistent with”; (10) council-derived questions added. Pages affected: 1 source page, state.md (5 new Watch Items, Current Focus updated)

[2026-05-14] schema-update | Added poppler fallback path to Council workflow

Change: CLAUDE.md §Workflows → Summon the Council → Step 2 now includes a hardcoded local fallback path for pdftoppm.exe (WinGet install location) when the command is not on PATH. Scope: CLAUDE.md §Workflows → Summon the Council Pages affected: 0 Reason: Poppler installed via WinGet but not on system PATH; fallback prevents unnecessary halts during council reviews.

[2026-05-14] schema-update | Added “Summon the Council” workflow

Change: New workflow in CLAUDE.md §Workflows — multi-agent critical review panel for papers. Architecture block updated to include Claude-council/ folder. Scope: CLAUDE.md §Architecture + §Workflows (new section after Remove/Merge Axis) Pages affected: 0 (reports-only workflow, no wiki page changes) Reason: Curator wants a structured multi-perspective critical review process for evaluating papers. First council review (Ansari2025) completed same session; workflow codified from that precedent.

[2026-05-14] council-review | Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue

Council: 4 members (Methodology Critic, Claims Validator, Contextual Critic, Strengths Advocate) + Council Head Output: Claude-council/raw thinking minutes-Ansari2025.md, Claude-council/council final report-Ansari2025.md Verdict: Landmark for Tph→IL-21→memory B cell axis identification. IL-21 blocking coculture is strongest evidence. scRNA-seq subclustering underpowered (n=4). DN2 identity inferred not confirmed. SHM paradox unresolved.

[2026-05-11] infra | Web deployment to Cloudflare Pages

efbwebshare/ — Quartz v4 setup (sibling of efb-dengue-wiki/), cloned from webforshare/ and adapted
efbwebshare/quartz.config.ts — pageTitle set to “EFB Dengue Literature Review”, baseUrl set to efb-dengue-wiki.pages.dev
efbwebshare/sync-and-build.ps1 — syncs efb-dengue-wiki/wiki/ → efbwebshare/content/, builds, commits, pushes
GitHub repo: OsandaC/efb-dengue-wiki (branch main)
Cloudflare Pages: efb-dengue-wiki.pages.dev
CLAUDE.md — added ### Update Web workflow
wiki/state.md — web deployment watch item resolved; decision recorded

[2026-05-11] deep lint | Full wiki health check (84 pages, 3 parallel agents)

Scope: All 84 pages scanned — sources (15), entities (41), concepts (7), methods (17), analyses (4). Three parallel sub-agents (sources, entities, concepts+methods+analyses) with manual cross-verification.

Structural health: CLEAN. Zero broken wikilinks, zero orphans, zero content displacement, zero insertion-order violations, zero frontmatter mismatches, 100% template compliance. All fixes from the 2026-05-08 deep lint have held.

New findings (1):

Source-listed-but-no-Key-Points pattern on high-source-count entity pages (IgA 7/4, IgD 9/3, CD38 13/6, CD27 12/7). Not violations per CLAUDE.md (source citation alone is acceptable), but noted as quality observation. Only actionable case: CD24/Scharer2019 (already tracked).

Still open from prior lints:

16 thin pages (8 entities + 8 methods) — expected to thicken with future ingests
B220 near-orphan (2 inbound links) — acceptable for minor marker
~10 early-ingest bullets missing evidence weight annotations (Wei2007/Tipton2015 era)
CD24/Scharer2019 missing Key Points bullet
External Citation Audit (54 papers) pending curator review
Curator Highlights empty (no ==highlights== in wiki pages)

[2026-05-10] ingest | Priyamvada2016 - Cross-Reactive Memory Plasmablasts in Secondary Dengue

Source: raw/priyamvada2016.pdf → Priyamvada2016 - Cross-Reactive Memory Plasmablasts in Secondary Dengue Created: 3 pages — source page, Original Antigenic Sin (concept), Antibody-Dependent Enhancement (concept) Updated: 16 linked pages — Plasmablast, Somatic Hypermutation, Memory B Cell, Extrafollicular Response, Class Switch Recombination, Germinal Center, IgG, IgM, IgA, CD19, CD20, CD27, CD38, Conventional Flow Cytometry, ELISpot, FACS Sorting, BCR Sequencing, FRNT Notable Finding: OAS demonstrated at mAb level — secondary DENV2 PBs preferentially neutralise DENV1 (entry #13) Citations: Semantic Scholar 116, CrossRef 106 (retrieved 2026-05-10) Key impact: Creates critical SHM tension with GodoyLozano2016 (high vs. low SHM); dual-pathway model (memory recall + EF) now supported; first functional OAS evidence; near-universal ADE in PB mAbs

[2026-05-10] revision | Research Plan — Revision 3

Scope: Updated analyses/Research Plan - DN B Cell Expansion in Dengue.md to incorporate molecular BCR evidence from GodoyLozano2016 (low SHM, IGHV bias, convergent CDRH3s) and Appanna2016 (PB/MBC clonal disconnect, VH4-34 autoreactivity, CD27⁺ gate limitation). Changes: New “Molecular evidence from BCR sequencing” subsection in Background; rationale reframed around three converging evidence layers (cellular, molecular, clonal); Follow-Up Study 4 sharpened with 5 specific falsifiable predictions; interpretation framework updated with molecular predictions; Appanna2016 CD27⁺ gate limitation positioned as study-design strength; Sources Used expanded (+3). State.md updated.

[2026-05-10] deep lint | post-GodoyLozano2016/Appanna2016 health check

Scope: Full wiki scan — 14 sources, 41 entities, 5 concepts, 17 methods, 4 analyses (81 pages). Three parallel sub-agents (sources, entities+concepts, methods+analyses).

Issues found and fixed:

Category	Count	Details
Index source count mismatches	8	IgG (10→11), IRF4 (3→4), TLR7 (2→3), Extrafollicular Response (13→14), Germinal Center (12→13), Memory B Cell (13→14), Somatic Hypermutation (12→13), Class Switch Recombination (11→12). All off by 1 from GodoyLozano2016 ingest.
Duplicate source listings	3 pages	CD20 (GarciaBates2013 ×2), CD27 (GarciaBates2013 ×2), CD38 (Wrammert2012 ×2 + GarciaBates2013 ×2). Removed duplicates.
Missing template section	1 page	CD24 missing `## Contradictions & Debates`. Added.
Insertion-order violation	1 page	CXCR3 had a Key Point (dengue PB CXCR3⁺) misplaced inside Contradictions & Debates section. Moved to Key Points.
Missing forward link	1 source	Tipton2015 missing `[[Memory B Cell]]` from Concepts Addressed. Added.
Unreconciled contradiction	1	GodoyLozano2016 (globally low SHM in acute dengue IgG) vs. Appanna2016 (comparable SHM between sorted PBs and MBCs). Surfaced in Somatic Hypermutation Contradictions & Debates with methodological reconciliation.

Remaining (not fixable without new ingests):

17 thin pages (sources: 1): 8 entities (B220, CD23, CD71, ATF3, EGR, HOPX, Peripheral Helper T Cell, TOX2) + 9 methods (Spectral FCM, RRBS, Phospho-Flow, Serum Proteomics, AIM Assay, scRNA-seq, T-B Coculture, PRNT, FRNT).
~15 Key Points bullets across early-ingested pages (Wei2007, Tipton2015) lack evidence weight annotations (study type + sample size). Systematic but low-priority.
CD24 lists Scharer2019 in Sources but has no Key Points bullet citing it (source was added during Scharer2019 ingest but no content was written).
Wrammert2012 lists ELISA as plain text without wikilink (no ELISA method page exists).
Curator Highlights empty (no ==highlights== in wiki pages).

[2026-05-09] ingest | GodoyLozano2016 - Lower IgG SHM Rates in Acute Dengue

Source: raw/godoy-lozano2016.pdf (DOI: 10.1186/s13073-016-0276-1) Pages created: 1 (source page) Pages updated: 10 (3 entities: Plasmablast, IgG, TLR7; 5 concepts: Somatic Hypermutation, Extrafollicular Response, Germinal Center, Class Switch Recombination, Memory B Cell; 1 method: BCR Sequencing; 1 analysis: Notable Findings) Notable Finding added: SHM paradoxically lower in secondary than primary dengue — the opposite of affinity maturation. Citations: Semantic Scholar 42, CrossRef 44 (retrieved 2026-05-09).

[2026-05-09] ingest | Appanna2016 - Plasmablasts as Subset of Memory B Cell Pool

Source: raw/Appanna2016.pdf (DOI: 10.1016/j.ebiom.2016.09.003) Pages created: 1 (source page) Pages updated: 17 (9 entities: Plasmablast, CD19, CD20, CD27, CD38, CD138, IgG, IgM, IgA; 5 concepts: Memory B Cell, Somatic Hypermutation, Extrafollicular Response, Germinal Center, Class Switch Recombination; 3 methods: BCR Sequencing, FACS Sorting, Conventional Flow Cytometry) Notable Finding added: PB/MBC clonal disconnect — plasmablasts and DENV-binding MBCs are clonally unrelated and target different viral proteins. Citations: Semantic Scholar 57, CrossRef 60 (retrieved 2026-05-09).

[2026-05-08] schema-update | insertion-order guard + sub-agent lint note

Change: Added two workflow notes to CLAUDE.md: (1) insertion-order guard in Ingest steps 5–7 requiring new Key Points to be inserted into ## Key Points from Literature, not appended at end-of-file; (2) sub-agent parallelism note in Lint workflow recommending parallel Agent tool usage for deep lints. Scope: CLAUDE.md §Workflows → Ingest (propagation check block) and §Workflows → Lint (context-scaling note block). Pages affected: 0 (workflow guidance only). Reason: Root cause prevention — the content-after-Related-Pages displacement found on 19 pages during the deep lint was caused by end-of-file appending during ingests. Sub-agent note codifies the efficient lint pattern validated in the same session.

[2026-05-08] deep lint | post-landmark-ingests health check

Scope: Full wiki scan — 12 sources, 41 entities, 5 concepts, 17 methods, 4 analyses (79 pages).

Issues found and fixed:

Category	Count	Details
Content-after-Related-Pages displacement	19 pages	Key Points bullets appended after `## Related Pages` instead of under `## Key Points from Literature`. Fixed on 12 entity pages + 4 concept pages + 3 method pages.
Missing `## Contradictions & Debates` section	43 pages	Added placeholder on 29 entity pages + 14 method/concept pages.
Frontmatter source count mismatches	3 pages	FACS Sorting (5→6), In Vitro B Cell Stimulation (3→4), ELISpot (5→6).
Index header counts wrong	3 fields	Entities 40→41, Methods 16→17, Total 76→79.
Broken wikilinks	2	`[[ADE]]` and `[[CD45]]` in Research Plan — converted to plain text / removed.
Memory B Cell misclassified as entity	5 sources	Removed from Entities Mentioned in Anolik2004, Tipton2015, Woodruff2020, GarciaBates2013, Singh2026 (already in Concepts Addressed).
Singh2026 erroneous FACS Sorting link	1	Removed `[[FACS Sorting]]` (“not used”) from Methods Used.
Missing concept links in source pages	2 sources	Added `[[Somatic Hypermutation]]` + `[[Germinal Center]]` to Wrammert2012; `[[Somatic Hypermutation]]` to GarciaBates2013.
Notable Findings heading misplaced	1	`# Notable Findings` heading moved from mid-file to top; frontmatter blank lines fixed.
Orphan pages	2	Added `[[B220]]` to Double-Negative B Cell Related Pages; `[[CD10]]` to Activated Naive B Cell Related Pages.

Remaining (not fixable without new ingests):

17 thin pages (sources: 1) — 8 entities + 9 methods. Expected to thicken with future ingests.
Woodruff2020 links ELISpot and In Vitro B Cell Stimulation as “referenced” methods — minor inflation, left as-is.
Curator Highlights empty (no ==highlights== in wiki pages).

[2026-05-08] ingest | Parameswaran2013 - Convergent Antibody Signatures in Dengue

FIRST BCR REPERTOIRE INGEST — first VH sequencing data from dengue patients; convergent CDR3 evolution; intermediate SHM.

Pages created (1):

sources/Parameswaran2013 - Convergent Antibody Signatures in Dengue.md — n=60 dengue (Nicaraguan pediatric cohorts, DENV-2/DENV-3); 454 pyrosequencing of VH from unsorted PBMC gDNA; convergent CDR3s (10-mer/13-mer) shared across individuals; 4.4–6.9% V mutation = memory-derived; higher clonality in secondary dengue; multiple V gene families encode same CDR3; AUC 0.834 for dengue classification

Pages updated (6):

methods/BCR Sequencing.md (MAJOR: 454 pyrosequencing from gDNA; P(collision) clonality metric; convergent CDR3 cross-validation; multiple V gene usage; sources 4→5)
concepts/Somatic Hypermutation.md (FIRST DENGUE BCR DATA: 4.4–6.9% V mutation; intermediate between EF and GC benchmarks; sources 10→11)
concepts/Memory B Cell.md (convergent CDR3s from affinity-matured memory B cells; higher clonality in secondary = memory recall signature; sources 11→12)
concepts/Extrafollicular Response.md (intermediate SHM data relevant to EF vs GC origin; sources 11→12)
concepts/Germinal Center.md (mutation levels compatible with prior GC transit; sources 10→11)
analyses/Notable Findings.md (+1 entry: convergent CDR3 evolution across patients)

Citations: Semantic Scholar 260 | CrossRef 261 (retrieved 2026-05-08)

Notable finding added: Convergent CDR3 amino acid sequences shared across dengue patients, encoded by different V gene families — true convergent antibody evolution. First BCR-level mutation data from dengue: 4.4–6.9% V gene mutation, intermediate between EF and GC benchmarks.

[2026-05-08] ingest | Wrammert2012 - Plasmablast Responses in Acute Dengue

FOUNDATIONAL INGEST — first systematic characterisation of acute dengue plasmablast response; establishes magnitude/kinetics/specificity benchmarks.

Pages created (1):

sources/Wrammert2012 - Plasmablast Responses in Acute Dengue.md — n=46 confirmed dengue (Bangkok, 2009–2011); 47% of B cells; >1,000-fold expansion; day 6–7 peak; ≥70% DENV-specific IgG by ELISpot; cross-serotype reactive; no severity correlation (confounded); no hypergammaglobulinemia

Pages updated (15):

entities/Plasmablast.md (magnitude benchmark; DENV-specificity; no severity correlation; sources 10→11)
entities/CD19.md (CD19⁺ primary gate; sources 10→11)
entities/CD20.md (CD20⁻/low PB gate; sources 4→5)
entities/CD27.md (CD27^high PB gate; sources 9→10)
entities/CD38.md (CD38^high PB gate; sources 10→11)
entities/IgG.md (IgG dominance; no hypergammaglobulinemia; sources 8→9)
entities/IgM.md (IgM near-absent in secondary; sources 4→5)
entities/IgA.md (IgA minor component; sources 4→5)
concepts/Extrafollicular Response.md (magnitude benchmark; short-lived PB model; sources 10→11)
concepts/Memory B Cell.md (anamnestic recall evidence; sources 10→11)
concepts/Class Switch Recombination.md (IgG:IgM ratio confirms CSR; sources 9→10)
concepts/Somatic Hypermutation.md (gap flagged — no BCR data; sources 9→10)
methods/Conventional Flow Cytometry.md (5-color panel details; sources 10→11)
methods/ELISpot.md (first DENV ELISpot protocol; sources 4→5)
analyses/Notable Findings.md (+1 entry: no hypergammaglobulinemia despite massive PB)

Citations: Semantic Scholar 250 | CrossRef 242 (retrieved 2026-05-08)

[2026-05-08] ingest | GarciaBates2013 - Plasmablast Response and Dengue Severity

LANDMARK INGEST — first severity-stratified plasmablast quantification in dengue; earliest independent confirmation of neutralizing Ab paradox.

Pages created (2):

sources/GarciaBates2013 - Plasmablast Response and Dengue Severity.md — n=84 hospital-based dengue cohort (Recife, Brazil, 2004–2006); 46% mean / 87% peak plasmablasts in severe 2° dengue; >70% DENV-specific by ELISpot; serotype cross-reactive (3-fold infecting-serotype preference); PRNT₅₀ disconnect; B cell apoptosis (60% caspase-3⁺)
methods/PRNT.md — plaque reduction neutralization test; PRNT₅₀ on Vero cells; no plasmablast correlation

Pages updated (19):

entities/Plasmablast.md (severity-stratified data; DENV-specificity; cross-reactivity; PRNT₅₀ disconnect; apoptosis; sources 9→10)
entities/CD19.md (source added; sources 9→10)
entities/CD20.md (CD20⁻ dengue PB gate; sources 3→4)
entities/CD27.md (CD27⁺CD21⁻ PB/activated memory gate; sources 8→9)
entities/CD38.md (source added; sources 9→10)
entities/CD21.md (CD21⁺ naive identification; naive contraction in 2° DFC; sources 5→6)
entities/IgD.md (source added; sources 8→9)
entities/IgG.md (DENV-specific IgG without neutralization; sources 7→8)
entities/CD10.md (CD10⁻ mature B cell gate in dengue; sources 2→3)
entities/Double-Negative B Cell.md (source added; sources 9→10)
concepts/Extrafollicular Response.md (plasmablast severity biomarker; PRNT₅₀ disconnect; B cell apoptosis; sources 9→10)
concepts/Germinal Center.md (source added; sources 9→10)
concepts/Memory B Cell.md (source added; sources 9→10)
concepts/Somatic Hypermutation.md (source added; sources 8→9)
concepts/Class Switch Recombination.md (source added; sources 8→9)
methods/Conventional Flow Cytometry.md (GarciaBates2013 panel; LSRII; IgD omission noted; sources 9→10)
methods/ELISpot.md (DENV-specific ELISpot protocol; sources 3→4)
methods/FRNT.md (PRNT cross-reference added to Related Pages)
analyses/Notable Findings.md (1 new entry: plasmablast magnitude ↔ severity + neutralizing Ab disconnect)

Citations: Semantic Scholar 29, CrossRef 90 (retrieved 2026-05-08)

Notable finding added: Plasmablast magnitude scales with dengue severity (46% mean, 87% peak in 2° DFC) but does not predict neutralizing Ab titers — earliest independent confirmation of the neutralizing Ab paradox, 7 years before Woodruff2020 (COVID-19) and 12 years before Ansari2025 (dengue FRNT₅₀).

[2026-05-08] update | Research Plan — incorporated Ansari2025

Updated Research Plan - DN B Cell Expansion in Dengue.md (Revision 2) to incorporate Ansari2025 findings. Key changes: reframed rationale from exploratory discovery to quantitative confirmation in a second endemic population; added “Evidence from dengue (Ansari2025)” subsection; updated “dengue gap” to “remaining gap”; added H4 (DN2–plasmablast correlation); elevated DN2–plasmablast correlation to secondary outcome; updated interpretation framework for corroborative vs. contradictory findings; added Tph quantification as follow-up study 7; added Ansari2025 to Sources Used and Related Pages.

[2026-05-08] deep lint | Ansari2025 propagation check

Scope: Full propagation check of the Ansari2025 ingest, which was interrupted by API errors.

Checked: All 22 entity pages, 5 concept pages, and 8 method pages linked from the Ansari2025 source page.

Issues found and fixed (4):

T-bet entity page — propagation failure. Was NOT visited during ingest. Added: Ansari2025 source line, Key Points bullet (T-bet expected but not stained in dengue), frontmatter updated (sources: 4→5, updated date). Index updated.
Germinal Center concept page — missing Key Points bullet. Had Ansari2025 in Sources but no bullet about concurrent GC activity (CXCL13 elevation alongside Tph dominance). Added bullet.
Memory B Cell concept page — missing Key Points bullet. Had Ansari2025 in Sources but no bullet about Tph preferentially driving memory (not naive) B cell differentiation. Added bullet.
Conventional Flow Cytometry method page — missing panel details + frontmatter count. Had Ansari2025 in Sources but no bullet with T cell and B cell panel compositions. Added panel details bullet. Fixed frontmatter sources: 8→9.

Verified clean (no issues): Peripheral Helper T Cell, IL-21, Double-Negative B Cell, DN2 B Cell, Plasmablast, PD-1, CD21, CD11c, CXCR5, CXCR3, CD38, CD27, IgD, IgG, CD19, CD20, HOPX, TOX2, CD40L, CD71, Extrafollicular Response, Somatic Hypermutation, Class Switch Recombination, FACS Sorting, ELISpot, In Vitro B Cell Stimulation, Activation-Induced Marker Assay, Single-Cell RNA Sequencing, T-B Coculture Assay, FRNT.

[2026-05-08] note | Ansari2025 ingest interrupted by API errors

Context: The Ansari2025 ingest — the most important paper in this wiki (first direct evidence of EF B cell activation in dengue) — was interrupted multiple times by Claude API internal server errors. The conversation context was compacted mid-ingest, requiring reconstruction from a session summary. While the ingest was completed, some updates may be incomplete or inconsistent due to the interruptions. A deep and careful lint is recommended at the start of the next session to verify: (1) all entity/concept/method pages linked from the source page were actually visited, (2) frontmatter source counts match actual Sources lists, (3) no content was duplicated or lost during context compaction, (4) concept pages (GC, Memory B Cell, SHM, CSR) received substantive Ansari2025 content (not just source-line additions).

[2026-05-08] ingest | Ansari 2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue

LANDMARK INGEST — first direct evidence of extrafollicular B cell activation in dengue.

Pages created (10):

sources/Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue.md — n=170 acute dengue adults; CXCR5⁻PD-1⁺ Tph cells (~75% of activated CD4⁺); IL-21-dependent memory B cell→PB; CD21⁻CD11c⁺ EF B cells; scRNA-seq/TCR-seq; neutralizing Ab paradox
entities/Peripheral Helper T Cell.md (new: CXCR5⁻PD-1⁺ CD4⁺ T cell; IL-21⁺ helper vs GZMB⁺ cytotoxic subclusters)
entities/IL-21.md (new: key EF differentiation cytokine; Tph-derived; ~60% of PB output IL-21-dependent)
entities/HOPX.md (new: marks cytotoxic Tph subcluster)
entities/TOX2.md (new: marks helper Tph subcluster)
entities/CD40L.md (new: CD154; T-B costimulation; inhibits EF from naive; expressed on Tph)
entities/CD71.md (new: transferrin receptor; proliferation marker on dengue PBs)
methods/Activation-Induced Marker Assay.md (new: AIM assay for DENV-specific T cells)
methods/Single-Cell RNA Sequencing.md (new: 10x scRNA-seq + scTCR-seq)
methods/T-B Coculture Assay.md (new: Tph-driven B cell differentiation)
methods/FRNT.md (new: focus reduction neutralization test)

Pages updated (24):

entities/Double-Negative B Cell.md (CD21⁻CD11c⁺ EF B cells in dengue; Tph-IL-21 axis)
entities/DN2 B Cell.md (first dengue evidence of CD21⁻CD11c⁺ within DN gate)
entities/Plasmablast.md (full dengue PB phenotype; Tph-driven; neutralizing Ab paradox)
entities/PD-1.md (defining marker of Tph; PD-1⁺ on both Tph and DN2)
entities/CXCR5.md (Tph CXCR5⁻; CXCL13 elevated despite Tph dominance)
entities/CXCR3.md (CXCR3⁺ on dengue plasmablasts)
entities/CD21.md (CD21⁻ marks EF B cells in dengue)
entities/CD11c.md (CD11c⁺ marks EF B cells in dengue)
entities/IgG.md (anti-NS1/anti-prM IgG elevated in severe dengue; no increased neutralization)
entities/CD19.md (source added)
entities/CD20.md (source added)
entities/CD38.md (source added)
entities/CD27.md (source added)
entities/IgD.md (source added)
concepts/Extrafollicular Response.md (MAJOR: first dengue EF evidence; Tph mechanism; concurrent EF+GC; memory B cell preference; severity association)
concepts/Germinal Center.md (source added; concurrent GC activity via CXCL13)
concepts/Memory B Cell.md (source added; Tph preferentially drive memory B cells)
concepts/Somatic Hypermutation.md (source added)
concepts/Class Switch Recombination.md (source added)
methods/Conventional Flow Cytometry.md (source added)
methods/FACS Sorting.md (source added)
methods/ELISpot.md (source added)
methods/In Vitro B Cell Stimulation.md (source added)
analyses/Notable Findings.md (1 new entry: first EF evidence in dengue + Tph dominance)

Partially completed updates (deferred to next session):

Concept pages (Germinal Center, Memory B Cell, SHM, CSR): source added but substantive Ansari2025 content not yet added to Key Points sections
Method pages (Conventional Flow Cytometry): Ansari2025 panel details not yet added
T-bet, BLIMP-1: source not added (mentioned in source page but not directly stained)

Citations: Semantic Scholar 7, CrossRef 10 (retrieved 2026-05-08)

Notable finding added: First direct evidence of EF B cell activation in dengue — Tph cells (not Tfh) drive the response via IL-21. Neutralizing Ab paradox replicated in dengue. Concurrent EF+GC activity challenges antagonistic model.

[2026-05-08] lint | Deep lint + External Citation Audit

Critical finding: ~80 inline citations to 54 external (non-ingested) papers across ~25 entity/concept/method pages. Violates Rule 6. Two patterns: (A) 3 bare external citations with no ingested source attribution; (B) ~77 “citing X et al.” within (see [[SourcePage]]) patterns.

Pages created (1):

analyses/External Citation Audit.md — complete catalog of all 54 external papers: citation details, DOIs (26 confirmed, 7 verify, 21 not retrieved), ingested source of origin, and all wiki page locations with line numbers.

Pages updated (1):

index.md (analyses 3→4; total pages 61→62)

Other lint findings (unchanged from prior):

12 thin single-source pages (B220, CD20, CD23, CXCR3, ATF3, EGR, PD-1, SLAMF7, Spectral Flow Cytometry, RRBS, Phospho-Flow Cytometry, Serum Proteomics)
B220 near-orphan (only linked from Wei2007 + index)
No broken wikilinks
No frontmatter source count mismatches detected
No new orphan pages

Action pending: Curator to review External Citation Audit, verify accuracy of cited claims, decide which external papers to ingest vs. which citations to rewrite.

[2026-05-07] ingest | Scharer 2019 - Epigenetic Programming in SLE B Cells

Pages created (4):

sources/Scharer2019 - Epigenetic Programming in SLE B Cells.md — multi-omic (RRBS + ATAC-seq + RNA-seq) study of 5 B cell subsets from 9 SLE + 12 HC (all African-American females). Establishes epigenetic differentiation hierarchy and identifies T-BET/AP-1/EGR/ATF3 programmes in DN2.
entities/ATF3.md (new: stress-response TF; key SLE DN2-specific regulator; 98 target genes; ATF3-Jun heterodimerization)
entities/EGR.md (new: EGR1-4 family; EGR4 highest PageRank in SLE TF network; targets in 86% upregulated pathways)
entities/PD-1.md (new: PDCD1; ~60% PD-1⁺ on DN2; chromatin/mRNA/protein concordance)

Pages updated (26):

entities/DN2 B Cell.md (epigenetic characterization; T-BET/AP-1/EGR motifs; ATF3; PD-1; apoptosis resistance)
entities/T-bet.md (T-BET motifs in DN2 chromatin; autoregulatory loop; shared HC/SLE programme)
entities/Activated Naive B Cell.md (epigenetically closer to DN2 in SLE; AP-1/EGR accessibility; T3 state)
entities/Double-Negative B Cell.md (source added)
entities/BLIMP-1.md (PRDM1 progressive demethylation and accessibility)
entities/IRF4.md (source added)
entities/CD11c.md (source added)
entities/CD19.md (source added)
entities/Plasmablast.md (source added)
entities/CD27.md (source added)
entities/IgD.md (source added)
entities/CD38.md (source added)
entities/CD24.md (source added)
entities/CXCR5.md (source added)
concepts/Extrafollicular Response.md (epigenetic hierarchy; SLE disease signature in naive; T-BET normal vs AP-1/EGR disease-specific; ATF3; DN2 apoptosis resistance)
concepts/Germinal Center.md (SM vs DN2 epigenetic bifurcation — NF-κB/EBF vs T-BET/AP-1)
concepts/Memory B Cell.md (SM and DN2 share methylation but diverge epigenetically)
concepts/Somatic Hypermutation.md (epigenetic confirmation of EF vs GC origin)
concepts/Class Switch Recombination.md (PRDM1 progressive demethylation confirms EF CSR-competence)
methods/ATAC-seq.md (MAJOR: comprehensive multi-subset ATAC-seq; HOMER motifs; T-BET ChIP-seq integration; ATF3/PD-1 locus accessibility)
methods/RNA Sequencing.md (5,090 DEGs; PageRank TF network; EGR4 apex; ATF3 identification)
methods/RRBS.md (new method page — created during entity creation phase)
methods/Conventional Flow Cytometry.md (PD-1 and ATF3 intracellular validation)
methods/FACS Sorting.md (5-subset multi-omic sort design)
analyses/Notable Findings.md (1 new entry: SLE disease signature in resting naive B cells)
index.md (sources 7→8; entities 31→34; methods 10→11; total pages 57→61; description updates)

Citations: Semantic Scholar 155, CrossRef 172 (retrieved 2026-05-07)

Notable finding added: SLE disease signature already present in resting naive B cells (6,664 DMLs; NR4A1/NR4A3 upregulated indicating BCR+TLR engagement) — the EF pathway is epigenetically primed before activation. Reframes the stimulus-response model to a priming-plus-trigger model with direct implications for dengue endemic exposure.

[2026-05-06] ingest | Singh 2026 - DENV-Specific Memory B Cell Subsets

Pages created (1):

sources/Singh2026 - DENV-Specific Memory B Cell Subsets.md — first dengue-specific source in the wiki. Longitudinal pediatric cohort (n=18, 58 PBMC samples to 18M), DENV-specific MBC subsets by dual-labelled antigen probe flow cytometry, primary vs secondary infection.

Pages updated (19):

entities/Double-Negative B Cell.md (DENV-specific atypical MBC accumulation in 2° dengue; DN1/DN2/DN3 resolution limitation)
entities/Plasmablast.md (DENV IgM⁻ PB data)
entities/CD19.md (dengue B cell gating context)
entities/CD20.md (MBC vs PB gating in dengue)
entities/CD27.md (source added)
entities/CD21.md (source added)
entities/CD38.md (source added)
entities/IgD.md (source added)
entities/IgG.md (source added)
entities/IgM.md (source added)
entities/IgA.md (source added)
concepts/Memory B Cell.md (DENV-specific qualitative reprogramming; IgM+ recall; naïve-like persistence; delayed peaks)
concepts/Extrafollicular Response.md (atypical MBCs and IgM+ MBCs as potential EF memory in dengue)
concepts/Germinal Center.md (delayed DENV-specific MBC peaks)
concepts/Somatic Hypermutation.md (limited further SHM in flavivirus immunity)
concepts/Class Switch Recombination.md (DENV-specific class-switched MBC accumulation)
methods/Conventional Flow Cytometry.md (Singh2026 12-color panel; dual-labelled DENV antigen probes; 9 subset definitions)
analyses/Notable Findings.md (1 new entry: qualitative reprogramming finding)
index.md (sources 6→7; total pages 56→57; multiple description updates)

Citations: Semantic Scholar 0, CrossRef 0 (retrieved 2026-05-06; expected for recent preprint)

Notable finding added: Secondary dengue immunity = qualitative MBC reprogramming (not quantitative boost) — total DENV-specific B cells don’t differ by infection history, but specific subsets (IgG+, atypical, class-switched) are significantly higher. IgM+ MBCs are the only subset recalled during acute secondary infection.

[2026-05-06] revision | Research Plan - DN B Cell Expansion in Dengue (Revision 1)

Revision scope: Major protocol revision based on available reagents, setting constraints, and scope refinement.

Key changes:

Panel redesigned: 10-color → 12-marker/11-channel (RB705-CD19, PE-Cy7-CD66b, PE-CD11c, FITC-CD21, BV421-CD38, eFluor506-L/D, BV711-CD3/CD14 dump, BV785-IgD, APC-CD27, AF700-CD24, APC-Fire750-CD45). IgG/IgM removed (unavailable).
H4 (isotype distribution) moved to Follow-Up Studies.
Panel 2 (intracellular T-bet) removed from scope.
Sampling window: days 3–7 → days 5–9 post-fever-onset.
Healthy controls: dengue-naïve → seropositive (Sri Lanka is dengue-endemic; naïve subjects impractical).
PBMC isolation: Ficoll density gradient → BD FACS Lysing red cell lysis (whole blood staining).
Added: detailed compensation strategy (11 single-stain controls, spillover pair table), FMO protocol (8 FMOs with priority rankings), antibody titration protocol, staining protocol, instrument QC checklist.
Gating strategy updated: CD45 pre-gate, CD66b dump, CD24-based plasmablast/transitional B cell discrimination.
Limitations expanded (8 → 10 items). Follow-up studies expanded (4 → 6 items).

Pages updated (1):

analyses/Research Plan - DN B Cell Expansion in Dengue.md

[2026-05-06] analysis | Research Plan - DN B Cell Expansion in Dengue

Pages created (1):

analyses/Research Plan - DN B Cell Expansion in Dengue.md — detailed wet-lab protocol testing the hypothesis that IgD⁻CD27⁻ (DN) memory B cells expand in acute dengue. Includes: 10-color flow cytometry panel design with CD21/CD11c surrogate for DN1/DN2/DN3 subdivision (no CXCR5), three-group cross-sectional design (HC/DF/DHF, n=25/group), PBMC isolation protocol, gating strategy, sample size estimation, full statistical analysis plan, and follow-up study recommendations. Synthesised from Wei2007 (baseline benchmarks), Jenks2018 (DN subdivision logic), Woodruff2020 (infection comparator), Sanz2025 (nomenclature), and Tipton2015 (EF benchmarks).

Pages updated (1):

index.md — added analysis page, updated total page count to 56.

[2026-05-04] ingest | Woodruff 2020 - EF B Cell Responses in COVID-19

Pages created (3):

sources/Woodruff2020 - EF B Cell Responses in COVID-19.md
entities/CXCR3.md (new: IFN-γ-driven tissue homing receptor; CXCR5↓/CXCR3↑ switch on EF populations)
methods/Spectral Flow Cytometry.md (new: 24-marker Cytek Aurora panels; UMAP; standardised B cell definitions)

Pages updated (31):

entities/Double-Negative B Cell.md (DN composition in COVID-19 mirrors SLE; DN2:DN1 ratio; usM contraction)
entities/DN2 B Cell.md (first infection context; expansion in ICU; severity correlation; chemokine switch)
entities/DN3 B Cell.md (primary data from original description; significantly expanded in ICU; UMAP heterogeneity)
entities/Activated Naive B Cell.md (expanded in ICU; CD11c⁺ gating; T-bet expression validated)
entities/Plasmablast.md (massive ASC expansion; CD138⁺ enrichment; germline repertoire; neutralizing Ab paradox)
entities/CD11c.md (validated in infection; DN1/DN2/DN3 gating in 24-marker panel)
entities/CD138.md (CD138⁺ enrichment in ICU; UMAP cluster 3; CD138 on CD21lo Tr)
entities/CD21.md (CD21lo Tr expanded in outpatients; CD21 vs CD11c DN gating)
entities/CXCR5.md (CXCR5↓ on EF populations; CXCR5/CXCR3 reciprocal switch)
entities/T-bet.md (intracellular staining in COVID-19; UMAP colocalisation)
entities/IgG.md (IgG1 dominant; anti-RBD IgG; VH4-34/9G4 autoreactivity)
entities/IgM.md (source added)
entities/IgA.md (source added)
entities/CD19.md (source added)
entities/CD27.md (source added)
entities/CD38.md (source added)
entities/IgD.md (source added)
concepts/Extrafollicular Response.md (MAJOR: first infection validation; neutralizing Ab paradox; DN2-CRP correlation; GC suppression; dengue context expanded)
concepts/Germinal Center.md (GC loss in fatal COVID-19; timing not the driver)
concepts/Memory B Cell.md (usM contraction; DN1/sM UMAP overlay)
concepts/Somatic Hypermutation.md (>50% germline VH in COVID ASC; defective clonal redemption)
concepts/Class Switch Recombination.md (ongoing CSR in EF-derived COVID ASCs)
methods/Conventional Flow Cytometry.md (Table 1 standardised definitions; intracellular T-bet)
methods/BCR Sequencing.md (10x Chromium scV(D)J; GLaMST; Circos)
methods/FACS Sorting.md (ASC/naive sorting gates; CD138 enrichment)
entities/IRF4.md (source added; COVID-19 EF context)
entities/BLIMP-1.md (source added; PRDM1 pathway in COVID-19 EF ASCs)
methods/ELISpot.md (source added; referenced in COVID-19 context)
methods/In Vitro B Cell Stimulation.md (source added; referenced as foundational method)
index.md (sources 5→6; total pages 52→55; entities 30→31; methods 9→10; all descriptions updated)
analyses/Notable Findings.md (1 new entry: neutralizing Ab paradox)

Citations: Semantic Scholar 686, CrossRef 726 (retrieved 2026-05-04)

Notable finding added: EF-derived neutralizing antibodies correlate with death, not protection — functional class-switched neutralizing antibodies produced via germline-dominant EF pathway correlate with ICU admission and mortality in COVID-19. Paradox directly relevant to dengue ADE hypothesis.

[2026-05-03] ingest | Sanz 2025 - Human Atypical B Cells Overview

Pages created (3):

sources/Sanz2025 - Human Atypical B Cells Overview.md
entities/DN3 B Cell.md (new: CXCR5⁻CD21⁻CD11c⁻T-bet⁻ pre-plasmablast; distinct from DN2 and AtB/ABC)
entities/SLAMF7.md (new: CD319; DN2/aNAV/PC marker; therapeutic target approved for myeloma)

Pages updated (28):

entities/Double-Negative B Cell.md (DN3 subdivision; AtB label obsolete; CD27 modulation; context-dependent DN2)
entities/DN2 B Cell.md (memory DN2 exist; DN2/DN1 ratio as index; DN2 in RA synovium; ABC as APCs; exhaustion challenged)
entities/Activated Naive B Cell.md (largest ABC-phenotype source in primary responses; SLAMF7 in extended phenotype)
entities/Plasmablast.md (DN3 as pre-PB; DN2 in RA synovium)
entities/CD27.md (CD27 modulation; obsolete as sole memory marker)
entities/CD21.md (CD21lo heterogeneous; not reciprocal with CD11c)
entities/CD11c.md (heterogeneous across compartments; inducible without T-bet/IFN-γ)
entities/T-bet.md (not absolutely required for ABC; autoregulatory TBX21 locus; memory partition)
entities/CXCR5.md (substitutable for CD21 in gating)
entities/FCRL5.md (therapeutic target; memory partition; substitutable for CD11c)
entities/FcRH4.md (historical origin of “atypical memory” label)
entities/ZEB2.md (primary ABC driver; represses Mef2b; independent of T-bet)
entities/IRF4.md (IRF4 motifs in ABC chromatin)
entities/BLIMP-1.md (source added)
entities/BACH2.md (source added)
entities/TRAF5.md (source added)
entities/TLR7.md (TLR7 GoF mutations; indirect mutations; therapeutic inhibition)
entities/CD19.md (source added)
entities/CD38.md (source added)
entities/IgD.md (source added)
entities/IgG.md (source added)
concepts/Extrafollicular Response.md (EF/GC endotypes; self-limited autoreactivity; GC-independent autoimmunity; ZEB2/Mef2b; EF in HIV/cancer)
concepts/Germinal Center.md (ZEB2 represses Mef2b; GC-independent autoimmunity confirmed; ABC sustain GC paradox)
concepts/Memory B Cell.md (CD27 obsolete; memory DN2 exist; AtB label abandoned; memory vs. effector DN2 contradiction)
concepts/Somatic Hypermutation.md (SHM/CSR not restricted to GCs; partial RAG deficiency evidence)
concepts/Class Switch Recombination.md (CSR infrequent in GCs per Roco 2019)
methods/Conventional Flow Cytometry.md (Sanz2025 definitive classification; Table 1/Figure 2; IgD omission problem)
index.md (sources 4→5; total pages 49→52; entities 28→30; all descriptions updated)

Citations: Semantic Scholar 4, CrossRef 6 (retrieved 2026-05-03)

Notable finding added: The “atypical B cell” label conflates ≥5 distinct populations — context determines identity, not phenotype. Paradigm-level claim from the lab that defined the EF pathway. Direct implications for interpreting dengue AtB/ABC reports.

[2026-05-02] ingest | Jenks 2018 - DN2 B Cells and EF Pathway in SLE

Pages created (14):

sources/Jenks2018 - DN2 B Cells and EF Pathway in SLE.md
entities/DN2 B Cell.md (new: IgD⁻CD27⁻CXCR5⁻CD21⁻CD11c⁺ EF pre-plasmablast)
entities/T-bet.md (new: TBX21 TF; highest in DN2/aNAV)
entities/CD11c.md (new: ITGAX; defining DN2 marker)
entities/CXCR5.md (new: follicle-homing receptor; absence defines DN2)
entities/FCRL5.md (new: FCRL4⁻/FCRL5⁺ pattern)
entities/ZEB2.md (new: cooperates with T-bet)
entities/IRF4.md (new: PC differentiation TF)
entities/BLIMP-1.md (new: PRDM1; open chromatin by ATAC-seq in DN2)
entities/BACH2.md (new: repressor; absent in DN2)
entities/TRAF5.md (new: negative TLR regulator; explains dual TLR7/CD40L phenotype)
entities/TLR7.md (new: ssRNA sensor; EF differentiation driver)
methods/RNA Sequencing.md (new: 2,154 DEGs between B cell subsets)
methods/ATAC-seq.md (new: PRDM1 locus chromatin accessibility)
methods/Phospho-Flow Cytometry.md (new: pERK/pMAPKp38 TLR7 readout)

Pages updated (20):

entities/Double-Negative B Cell.md (DN1/DN2 subdivision; EF origin resolved; relationship to atypical B cells)
entities/Activated Naive B Cell.md (shared identity with DN2; developmental link; CD40L/IL-4 inhibition)
entities/Plasmablast.md (DN2 as direct pre-PB; clonal connectivity; DN2/PC correlation)
entities/FcRH4.md (FCRL4⁻ on DN2; distinguishes from HIV exhausted memory)
entities/CD38.md (CD38⁻ defines DN2)
entities/CD19.md (CD19^hi defines DN2)
entities/IgG.md (lower sIgG on DN2; IgG3 enrichment)
entities/CD27.md (DN1/DN2 resolution of CD27⁻ memory puzzle)
entities/CD24.md (CD24⁻ shared by aNAV and DN2)
entities/IgD.md (IgD marks aNAV→DN2 transition)
concepts/Extrafollicular Response.md (major: complete pathway; TLR7 mechanism; antagonistic GC/EF regulation)
concepts/Germinal Center.md (DN1 GC-derived; CD40L promotes GC, inhibits EF)
concepts/Memory B Cell.md (DN1 as SWM precursor; DN2 is not memory)
concepts/Somatic Hypermutation.md (DN2 mutation rate; DN1/DN2 resolution)
concepts/Class Switch Recombination.md (IgG3 enrichment in DN2)
methods/Conventional Flow Cytometry.md (Jenks2018 DN1/DN2 panel; CXCR5 gating)
methods/FACS Sorting.md (DN1/DN2 sort strategy)
methods/BCR Sequencing.md (aNAV-DN2-PC clonal connectivity)
methods/In Vitro B Cell Stimulation.md (TLR7/IFN-γ/IL-21 EF system; DN2 autoantibody production)
methods/ELISpot.md (DN2 IgG ASC output)

Citations: Semantic Scholar 854, CrossRef 921 (retrieved 2026-05-02)

Notable finding added: GC and EF pathways are antagonistically regulated — CD40L blocks EF, TLR7 blocks GC — mediated by TRAF5 deficiency in DN2/aNAV cells. Direct implications for dengue TLR7 biology.

[2026-05-02] lint | Full health check

Issues found & fixed (5):

entities/CD10.md — frontmatter sources: 1 → corrected to sources: 2 (body lists Wei2007 + Tipton2015)
entities/IgG.md — frontmatter sources: 1 → corrected to sources: 2 (body lists Wei2007 + Tipton2015)
entities/IgM.md — frontmatter sources: 1 → corrected to sources: 2 (body lists Wei2007 + Tipton2015)
entities/IgA.md — frontmatter sources: 1 → corrected to sources: 2 (body lists Wei2007 + Tipton2015)
methods/FACS Sorting.md — frontmatter sources: 1 → corrected to sources: 2 (body cites Wei2007 + Tipton2015)
concepts/Class Switch Recombination.md — frontmatter sources: 1 → corrected to sources: 2 (body cites Wei2007 + Tipton2015)
methods/Conventional Flow Cytometry.md — duplicated “Related Pages” section removed

Structural issues (not fixed — cosmetic):

11 of 18 entity pages missing “Contradictions & Debates” section (expected for thin single-source pages with nothing to debate yet)

Thin pages (sources < 2 after corrections):

Entities: FcRH4, B220, CD20, Activated Naive B Cell, CD138, CD21, CD23 (all single-source)
Methods: In Vitro B Cell Stimulation, ELISpot, Serum Proteomics (all single-source)

Orphan check: No true orphans — all pages have at least one inbound link from source pages + index. B220 is nearly orphaned (linked only from Wei2007 source page and index; no entity/concept pages link to it).

Broken links: None detected. All wikilinks resolve to existing pages.

Curator Highlights: No active highlights found. Page remains empty (as expected).

No contradictions between pages detected.

[2026-05-02] ingest | Tipton 2015 - ASC Diversity and Origin in SLE

Pages created (7):

sources/Tipton2015 - ASC Diversity and Origin in SLE.md
entities/Activated Naive B Cell.md (new entity: acN cells — EF ASC precursors)
entities/CD138.md (new: plasmablast maturation marker; CD138⁻/CD138⁺ ASC distinction)
entities/CD21.md (new: complement receptor; CD21⁻ marks acN cells)
entities/CD23.md (new: low-affinity IgE receptor; CD23⁻ marks acN cells; longitudinal disease-activity proxy)
methods/ELISpot.md (new: antigen-specific ASC quantification)
methods/Serum Proteomics.md (new: LC-MS/MS antibody identification from NGS databases)

Pages updated (20):

entities/Plasmablast.md (CD138⁻/CD138⁺ distinction, Ki67⁺ status, polyclonality, acN cell precursors)
entities/Activated Naive B Cell.md — see above
entities/CD19.md (CD19^hi marks acN cells; upregulated on B cell activation)
entities/CD27.md (CD27^hi in ASC gate; Tipton2015 gating context)
entities/CD38.md (CD38^lo in acN cells; full ASC gate CD19⁺IgD⁻CD27^hiCD38^hi)
entities/IgD.md (IgD⁺ retained on acN cells; limitation of IgD as naive discriminator)
entities/CD24.md (CD24⁻ as critical discriminator of acN vs. transitional cells)
entities/CD10.md (CD10⁻ in acN cells; argued against transitional misclassification)
entities/IgM.md (IgM contribution to SLE ASCs; IgM memory as GC-independent first layer)
entities/IgG.md (IgG+IgA majority of ASC sequences; switched isotypes in low-SHM EF ASCs)
entities/IgA.md (IgA in SLE ASC pool)
entities/Double-Negative B Cell.md (distinction from acN cells; acN cells are primary ASC precursors)
concepts/Extrafollicular Response.md (major: naive→EF→ASC pathway, germline autoreactivity, SHM benchmarks, polyclonal bystander activation)
concepts/Somatic Hypermutation.md (quantitative SHM benchmarks EF vs. GC; germline autoreactivity without SHM)
concepts/Germinal Center.md (acN cells feed both EF and GC; IgM memory as GC-independent layer)
concepts/Memory B Cell.md (IgM-only memory as first GC-independent layer; acN cell as gateway state)
concepts/Class Switch Recombination.md (CSR in low-SHM EF-derived ASCs)
methods/BCR Sequencing.md (major: NGS approach, clonality metrics D20/D50, connectivity analysis, IgTree phylogenetics)
methods/Conventional Flow Cytometry.md (Tipton2015 panel; MTG/CD24 acN gating strategy)
methods/FACS Sorting.md (multi-population sort for simultaneous NGS connectivity analysis)

Citations: Semantic Scholar 374, CrossRef 526 (retrieved 2026-05-02)

Notable finding added: Germline-encoded VH4-34 antibody (zero VH and VL mutations) displays full lupus-specific autoreactivity — direct proof that EF naive→ASC differentiation produces pathologically relevant autoantibodies without SHM or GC transit.

[2026-05-02] ingest | Anolik 2004 - Rituximab and B Cell Abnormalities in SLE

Pages created (3):

sources/Anolik2004 - Rituximab and B Cell Abnormalities in SLE.md
methods/Bm Classification.md
entities/CD20.md

Pages updated (10):

entities/Double-Negative B Cell.md (DN expansion in independent cohort; autoantibody correlation; reversibility after depletion)
entities/Plasmablast.md (major: expansion data, CD20⁻ phenotype, short-lived kinetics, long-lived vs. short-lived dichotomy)
entities/CD38.md (plasmablast gate CD38^high CD19^low CD20⁻; pre-GC gate Bm2ʹ)
entities/CD19.md (CD19^low as plasmablast marker; Anolik2004 panel context)
methods/Conventional Flow Cytometry.md (Anolik2004 panel; combined IgD/CD27 + CD38/IgD strategy)
concepts/Extrafollicular Response.md (DN reversibility; plasmablast EF dynamics; disease severity correlation)
concepts/Germinal Center.md (pre-GC expansion; rituximab resistance; GC censoring defect)
concepts/Memory B Cell.md (autoreactive VH4.34 memory; residual switched memory after depletion)
analyses/Notable Findings.md (1 new entry: plasmablast short-lived kinetics)
index.md

Citations: Semantic Scholar 488, CrossRef 374 (retrieved 2026-05-02)

Notable finding added: Circulating plasmablasts decline rapidly after rituximab despite CD20⁻ phenotype — direct kinetic evidence of short-lived nature dependent on CD20⁺ precursor input; mechanistic benchmark for dengue acute plasmablast wave.

[2026-05-02] ingest | Wei 2007 - DN Memory B Cells in SLE

Pages created (23):

sources/Wei2007 - DN Memory B Cells in SLE.md
entities/Double-Negative B Cell.md, CD27.md, IgD.md, FcRH4.md, CD38.md, CD19.md, IgG.md, IgM.md, IgA.md, CD10.md, CD24.md, B220.md, Plasmablast.md
concepts/Extrafollicular Response.md, Germinal Center.md, Memory B Cell.md, Somatic Hypermutation.md, Class Switch Recombination.md
methods/Conventional Flow Cytometry.md, FACS Sorting.md, BCR Sequencing.md, In Vitro B Cell Stimulation.md

Pages updated (2): analyses/Notable Findings.md (1 new entry), index.md

Citations: Semantic Scholar 590, CrossRef 518 (retrieved 2026-05-02)

Notable finding added: Autoreactive 9G4 B cells distribute equally across DN and CD27⁺ memory compartments in SLE — implications for autoreactive/cross-reactive specificity in EF-derived dengue B cells.

Naming conventions established (first ingest): Entity pages use singular descriptive names (e.g., Double-Negative B Cell, Plasmablast, CD27). Source short titles follow AuthorYear - Short Descriptive Title format.

[2026-05-02] init | EFB Dengue Wiki scaffold created

Change: Initial wiki scaffold. Created CLAUDE.md, CLAUDE_UPDATE.md, wiki/{index,state,log}.md, empty wiki/analyses/{Notable Findings,Curator Highlights}.md, and empty subfolders raw/, wiki/{sources,entities,concepts,methods,analyses}/. Scope: Adapted from dengue-wiki/ template. Removed geography/ axis and Update Web workflow. Rewrote Domain Context for extrafollicular B cell dynamics in dengue (flow cytometry focus). Pages affected: none (no content yet) Reason: Curator initialising a focused literature review on a new research area — extrafollicular B cell dynamics in dengue.

EFB Dengue Literature Review

Explorer

log

Wiki Operation Log

[2026-06-29] ingest | Morra ME 2018 - Defining Warning Signs and Severe Dengue

[2026-06-29] ingest | Narvaez F 2011 - Evaluating WHO Dengue Severity Classifications

[2026-06-27] page | DN2 Gating Strategy — added canonical start→finish gating tree

[2026-06-27] page | Switched Memory B Cell entity created + DN2 Gating Strategy reconciled

[2026-06-27] schema-update | Voice (TTS) Mode workflow added to CLAUDE.md

[2026-06-26] prep | Pre-meeting reframe — prelim meeting is wiki-first, not pitch-first

[2026-06-25] prep | PhD meeting fact-check pass + corrections + cold rehearsal

[2026-06-25] ops | PhD upgrade pitch prep — meeting with Prof. Rukie and Prof. Neelika

[2026-06-25] consult | Gating strategy for rN/aN/usM/sM in 11-color panel

[2026-06-16] flowjo check | CD66b dump gate vs CD19+ spread (Specimen_001_HT 82_002.fcs)

[2026-06-14] new method page | DN2 Panel - Staining, Compensation, and Gating Protocol

[2026-06-14] new method page | Compensation and FMO Controls

[2026-06-14] consult | Compensation & CD11c-FMO cadence (11-color DN2 panel)

[2026-06-14] analysis | B Cell Panel Variant 1

[2026-06-14] analysis | Thesis Objectives and Grant Pitch

[2026-06-14] deep lint | Post-reframe + Lamprinou2026 health check (100 pages, 3 parallel agents)

[2026-06-14] ingest | Lamprinou2026 - ABCs and DN B Cells

[2026-06-13] reframe | Atypical B Cell umbrella + spine reframe (complete)

[2026-06-13] direction | New high-level direction + bridge-wiki created

[2026-05-24] revision | Research Plan - DN B Cell Expansion in Dengue → Revision 4

[2026-05-24] schema-update | CLAUDE.md refactor — lazy-load council, rename governance, trim fat

[2026-05-23] thicken | OAS and ADE concept pages — Category 5 thin page resolution

[2026-05-23] deep-lint-fix | Concepts folder — 4 categories, 24 fixes applied

[2026-05-22] ingest | Kaneko2020 - GC Loss and TFH Block in COVID-19

[2026-05-22] deep lint | Health check (90 pages, 18 sources)

[2026-05-22] ingest | Sutton2021 - Alternative Lineage B Cells in Vaccination and Infection

[2026-05-20] analysis | DN2 Gating Strategy

[2026-05-19] ingest | Bhattacharya2016 - Memory B Cell Subset Selection in Secondary Dengue

[2026-05-19] deep lint | Health Check

[2026-05-18] ingest | William2002 - Extrafollicular Somatic Hypermutation in Autoimmune Mice

[2026-05-18] council-directed edits | wiki/concepts/Extrafollicular Response.md

[2026-05-17] lint + council review | wiki/concepts/Extrafollicular Response.md

[2026-05-15] council review | Jenks2018 - DN2 B Cells and EF Pathway in SLE

[2026-05-15] council review | Sanz2025 - Human Atypical B Cells Overview

[2026-05-15] council review | Woodruff2020 - EF B Cell Responses in COVID-19

[2026-05-14] deep lint | Council-augmented deep lint (8 parallel agents + advisor)

[2026-05-14] ops | Web deployment updated — council folder added to sync

[2026-05-14] ops | Cloudflare Pages reconnect and redeploy

[2026-05-14] council-update | Ansari2025 source page updated from council findings

[2026-05-14] schema-update | Added poppler fallback path to Council workflow

[2026-05-14] schema-update | Added “Summon the Council” workflow

[2026-05-14] council-review | Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue

[2026-05-11] infra | Web deployment to Cloudflare Pages

[2026-05-11] deep lint | Full wiki health check (84 pages, 3 parallel agents)

[2026-05-10] ingest | Priyamvada2016 - Cross-Reactive Memory Plasmablasts in Secondary Dengue

[2026-05-10] revision | Research Plan — Revision 3

[2026-05-10] deep lint | post-GodoyLozano2016/Appanna2016 health check

[2026-05-09] ingest | GodoyLozano2016 - Lower IgG SHM Rates in Acute Dengue

[2026-05-09] ingest | Appanna2016 - Plasmablasts as Subset of Memory B Cell Pool

[2026-05-08] schema-update | insertion-order guard + sub-agent lint note

[2026-05-08] deep lint | post-landmark-ingests health check

[2026-05-08] ingest | Parameswaran2013 - Convergent Antibody Signatures in Dengue

[2026-05-08] ingest | Wrammert2012 - Plasmablast Responses in Acute Dengue

[2026-05-08] ingest | GarciaBates2013 - Plasmablast Response and Dengue Severity

[2026-05-08] update | Research Plan — incorporated Ansari2025

[2026-05-08] deep lint | Ansari2025 propagation check

[2026-05-08] note | Ansari2025 ingest interrupted by API errors

[2026-05-08] ingest | Ansari 2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue

[2026-05-08] lint | Deep lint + External Citation Audit

[2026-05-07] ingest | Scharer 2019 - Epigenetic Programming in SLE B Cells

[2026-05-06] ingest | Singh 2026 - DENV-Specific Memory B Cell Subsets

[2026-05-06] revision | Research Plan - DN B Cell Expansion in Dengue (Revision 1)

[2026-05-06] analysis | Research Plan - DN B Cell Expansion in Dengue

[2026-05-04] ingest | Woodruff 2020 - EF B Cell Responses in COVID-19

[2026-05-03] ingest | Sanz 2025 - Human Atypical B Cells Overview

[2026-05-02] ingest | Jenks 2018 - DN2 B Cells and EF Pathway in SLE

[2026-05-02] lint | Full health check

[2026-05-02] ingest | Tipton 2015 - ASC Diversity and Origin in SLE

[2026-05-02] ingest | Anolik 2004 - Rituximab and B Cell Abnormalities in SLE

[2026-05-02] ingest | Wei 2007 - DN Memory B Cells in SLE

[2026-05-02] init | EFB Dengue Wiki scaffold created

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