EFB Dengue Literature Review

index

9 min read

EFB Dengue Wiki — Master Index

Last updated: 2026-05-10 | Sources: 15 | Total pages: 84

Sources (15)

PageYearJournalDisease Context
Wrammert2012 - Plasmablast Responses in Acute Dengue2012J VirolDengue (FOUNDATIONAL: first systematic PB characterisation; 47% of B cells; >1,000-fold expansion; day 6–7 peak; ≥70% DENV-specific IgG; cross-serotype reactive; no severity correlation [confounded])
Parameswaran2013 - Convergent Antibody Signatures in Dengue2013Cell Host MicrobeDengue (FIRST BCR REPERTOIRE: convergent CDR3s across patients; 4.4–6.9% V mutation = memory-derived; higher clonality in secondary; convergent evolution from multiple V genes; n=60)
GarciaBates2013 - Plasmablast Response and Dengue Severity2013J ImmunolDengue (LANDMARK: severity-stratified plasmablast data; 46% mean/87% peak in 2° DFC; >70% DENV-specific; serotype cross-reactive; plasmablast-PRNT₅₀ disconnect; B cell apoptosis)
Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue2025Cell ReportsDengue (LANDMARK: first EF B cell evidence; Tph→IL-21→memory B cell→plasmablast; CD21⁻CD11c⁺ DN expansion; severity association; neutralizing Ab paradox)
Appanna2016 - Plasmablasts as Subset of Memory B Cell Pool2016EBioMedicineDengue (CLONAL DISCONNECT: PBs and DENV-binding MBCs clonally unrelated; PBs 85% E-specific, MBCs 56% complex epitope; VH4-34 enrichment in PBs; IgM-dominant DENV-binding MBCs; n=12)
Priyamvada2016 - Cross-Reactive Memory Plasmablasts in Secondary Dengue2016J VirolDengue (OAS + ADE: 53 mAbs from sorted 2° DHF PBs; 70% E-specific, all cross-reactive; 45/53 ADE-competent; OAS in 2/4 patients — DENV1 neutralised over infecting DENV2; mean 18.1 VH mutations = memory origin; n=4 2° DHF)
GodoyLozano2016 - Lower IgG SHM Rates in Acute Dengue2016Genome MedicineDengue (LANDMARK: first direct SHM measurement in dengue IgG plasmablasts; paradoxically low SHM in acute phase; lower in secondary than primary; lower in DWS+ than DWS−; IGHV1-2/1-69 bias; convergent CDRH3s at 52% prevalence; GC-independent pathway proposed; n=19)
Singh2026 - DENV-Specific Memory B Cell Subsets2026bioRxivDengue (DENV-specific MBC subsets; primary vs secondary; longitudinal to 18M)
Scharer2019 - Epigenetic Programming in SLE B Cells2019Nat ImmunolSLE (multi-omic epigenetics; RRBS + ATAC-seq + RNA-seq; T-BET/AP-1/EGR/ATF3 programmes)
Sanz2025 - Human Atypical B Cells Overview2025Immunol RevReview (AtB nomenclature, DN classification, cross-disease context)
Woodruff2020 - EF B Cell Responses in COVID-192020Nat ImmunolCOVID-19 (EF pathway in acute viral infection; DN2/aN/ASC expansion; neutralizing Ab paradox)
Jenks2018 - DN2 B Cells and EF Pathway in SLE2018ImmunitySLE (DN2 B cells, complete EF pathway, TLR7)
Tipton2015 - ASC Diversity and Origin in SLE2015Nat ImmunolSLE (ASC diversity, EF origin, acN cells)
Wei2007 - DN Memory B Cells in SLE2007J ImmunolSLE (comparative immunology baseline)
Anolik2004 - Rituximab and B Cell Abnormalities in SLE2004Arthritis RheumSLE (B cell homeostasis; rituximab trial)

Entities (41)

B Cell Subsets

  • Double-Negative B Cell — IgD⁻CD27⁻ memory B cells; DN1/DN2/DN3 subdivision; CD21⁻CD11c⁺ EF phenotype now confirmed in dengue (sources: 10)
  • DN2 B Cell — IgD⁻CD27⁻CXCR5⁻CD21⁻CD11c⁺CD19^hi; EF pre-plasmablast; first dengue evidence from Ansari2025 (sources: 5)
  • DN3 B Cell — IgD⁻CD27⁻CXCR5⁻CD21⁻CD11c⁻T-bet⁻; pre-plasmablast; first described in COVID-19 (sources: 2)
  • Plasmablast — CD20⁻CD38⁺⁺CD27⁺Ki67⁺CD71⁺CXCR3⁺; 47% of B cells/30% of lymphocytes (Wrammert2012); 46% mean/87% peak in severe 2° dengue; >70% DENV-specific; Tph-driven via IL-21; plasmablast–neutralization disconnect; clonally unrelated to co-circulating DENV-binding MBCs; high SHM + OAS + near-universal ADE (sources: 13)
  • Activated Naive B Cell — CD19^hi, MTG⁺/CD11c⁺, CD24⁻, CD21⁻; EF ASC precursor; epigenetically closer to DN2 in SLE (sources: 5)
  • Memory B Cell — see Concepts (foundational concept page)

T Cell Subsets

  • Peripheral Helper T Cell — CXCR5⁻PD-1⁺ CD4⁺; ~75% of activated CD4⁺ T cells in dengue; IL-21⁺ helper vs GZMB⁺ cytotoxic subclusters; drives memory B cell→PB differentiation (sources: 1)

Surface Markers & Receptors

  • CD19 — pan-B cell marker; CD19^hi marks DN2 and acN cells; CD19^lo marks plasmablasts (sources: 13)
  • CD20 — B cell marker lost on plasmablasts; rituximab target; PB gating in dengue (sources: 7)
  • CD21 — complement receptor; CD21⁻ defines EF populations; CD21⁻CD11c⁺ B cells expanded in dengue (sources: 6)
  • CD23 — low-affinity IgE receptor; CD23⁻ marks acN cells; disease-activity proxy (sources: 1)
  • CD24 — CD24⁻ shared by acN and DN2 cells; discriminates from transitional B cells (sources: 4)
  • CD27 — canonical memory marker; obsolete as sole memory marker; CD27 can be modulated (sources: 12)
  • CD38 — activation/differentiation marker; CD38^hi on plasmablasts; CD38⁺HLA-DR⁺ on activated T cells (sources: 13)
  • CD10 — transitional/GC marker; CD10⁻ on DN cells and acN cells; mature B cell gate in dengue (sources: 3)
  • CD11c — ITGAX integrin; defining marker of DN2/aNAV; CD11c⁺ EF B cells confirmed in dengue (sources: 5)
  • CD138 — plasmablast maturation marker; CD138⁺ enriched in severe COVID-19 ASCs; first dengue panel inclusion (sources: 3)
  • CD40L — CD154; T-B costimulation; inhibits EF pathway from naive cells; expressed on Tph in dengue (sources: 2)
  • CD71 — transferrin receptor; proliferation marker on dengue plasmablasts (sources: 1)
  • CXCR5 — follicle-homing receptor; absent on DN2 B cells and Tph T cells; CXCL13 elevated in dengue (sources: 5)
  • CXCR3 — IFN-γ-driven tissue homing; CXCR3⁺ on dengue plasmablasts and COVID-19 EF populations (sources: 2)
  • FCRL5 — Fc receptor-like 5; expressed on DN2/aNAV; therapeutic target candidate (sources: 2)
  • FcRH4 — inhibitory Fc receptor homolog; absent on circulating DN cells and DN2 (sources: 3)
  • SLAMF7 — CD319; expressed on DN2/aNAV/PC; therapeutic target (approved for myeloma) (sources: 2)
  • IgD — surface immunoglobulin; retained on acN cells; lost at DN2 transition; used for DN gating (sources: 9)
  • IgG — predominant switched isotype; DENV-specific IgG massive but non-neutralizing; anti-NS1/anti-prM elevated in severe dengue; PB IgG 85% E-specific and more neutralizing; near-universal ADE; OAS bias (sources: 12)
  • IgM — unswitched isotype; balanced with IgG1/IgA1 in COVID-19 ASC; ongoing CSR to switched isotypes; IgM-dominant in DENV-binding MBCs (sources: 7)
  • IgA — mucosal isotype; IgA1 in COVID-19 ASC repertoire; anti-RBD IgA elevated in severe COVID (sources: 7)
  • B220 — CD45R isoform; heterogeneous in memory B cells (sources: 1)

Transcription Factors & Signalling

  • T-bet — TBX21; highest in DN2/aNAV; T-BET motifs top enriched in DN2 chromatin; expected but not stained in dengue (sources: 5)
  • ZEB2 — primary driver of ABC formation; represses Mef2b (GC TF); cooperates with T-bet (sources: 2)
  • ATF3 — stress-response TF; key SLE DN2-specific regulator; 98 target genes (sources: 1)
  • EGR — EGR1-4 family; EGR4 highest PageRank in SLE network (sources: 1)
  • PD-1 — PDCD1; ~60% PD-1⁺ on DN2 B cells; defining marker of Tph T cells in dengue (sources: 2)
  • IRF4 — PC differentiation TF; high IRF4/low IRF8 ratio in DN2 (sources: 4)
  • BLIMP-1 — PRDM1-encoded; elevated in DN2/aNAV; progressive demethylation (sources: 4)
  • BACH2 — terminal differentiation repressor; absent in DN2/aNAV (sources: 2)
  • TRAF5 — negative TLR regulator; uniquely low in DN2/aNAV (sources: 2)
  • TLR7 — ssRNA sensor; TLR7 GoF causes SLE; monogenic + indirect mutations drive ABC/DN2 (sources: 3)
  • HOPX — marks cytotoxic GZMB⁺ Tph subcluster in dengue scRNA-seq (sources: 1)
  • TOX2 — marks IL-21⁺ helper Tph subcluster; Tfh-associated TF on CXCR5⁻ cells (sources: 1)

Cytokines

  • IL-21 — key EF differentiation cytokine; produced by Tph and Tfh; blocking reduces PB output ~60% in dengue (sources: 2)

Concepts (7)

  • Extrafollicular Response — FIRST DENGUE EVIDENCE: Tph→IL-21→memory B cell→PB axis; CD21⁻CD11c⁺ EF B cells; 47%/87% PB severity association; plasmablast–neutralization disconnect; concurrent EF+GC; intermediate SHM in dengue BCR data; PB/MBC clonal disconnect consistent with EF origin (sources: 15)
  • Germinal Center — canonical differentiation; SM vs DN2 epigenetic bifurcation; GC loss in fatal COVID-19; concurrent GC activity in dengue (CXCL13↑); convergent CDR3 mutation compatible with GC transit (sources: 14)
  • Memory B Cell — Tph preferentially drive memory (not naive) B cell→PB in dengue; DENV-specific qualitative reprogramming in 2°; convergent CDR3s from affinity-matured memory B cells; PBs non-representative subset of MBC pool; OAS = strongest functional evidence of memory origin (sources: 15)
  • Somatic Hypermutation — epigenetic confirmation of EF vs GC origin; >50% germline VH in COVID-19 ASCs; FIRST DENGUE BCR DATA: 4.4–6.9% V mutation in convergent CDR3-bearing cells; comparable SHM in clonally unrelated PBs and MBCs; paradoxically low in acute dengue, lower in secondary; HIGH SHM (18.1 VH) in sorted 2° PBs = memory origin (sources: 14)
  • Class Switch Recombination — EF CSR-competence confirmed; class-switched memory B cells are Tph responders in dengue; IgG-dominant PBs vs IgM-enriched DENV-binding MBCs (sources: 13)
  • Original Antigenic Sin — memory recall bias toward prior serotype; 2/4 patients preferentially neutralise DENV1 over infecting DENV2; OAS at mAb level (sources: 1)
  • Antibody-Dependent Enhancement — 45/53 dengue PB mAbs enhance infection regardless of neutralisation potency; ADE-competent IgG from memory recall; future-exposure risk (sources: 1)

Methods (17)

  • Spectral Flow Cytometry — 24-marker Cytek Aurora panels; UMAP; Woodruff2020 Table 1 standardised B cell definitions (sources: 1)
  • Conventional Flow Cytometry — multi-color panels; Wrammert2012 (5-color) + GarciaBates2013 + Appanna2016 + Ansari2025 + Priyamvada2016 dengue panels (sources: 13)
  • Bm Classification — IgD/CD38 Bm1–Bm5 developmental staging framework (sources: 2)
  • FACS Sorting — multi-population sort for multi-omic profiling; antigen-specific live virus sorting; activated CD4⁺ T cell sorting for scRNA-seq (sources: 8)
  • BCR Sequencing — Sanger, NGS, 10x Chromium scV(D)J, 454 pyrosequencing; germline-dominant repertoire in COVID-19 EF ASCs; first dengue BCR data (Parameswaran2013); PB/MBC clonal overlap analysis; ImmunediveRsity pipeline + Monte Carlo deconvolution (sources: 8)
  • RNA Sequencing — 5,090 DEGs; PageRank TF network; EGR4 apex; ATF3 DN2-specific (sources: 2)
  • ATAC-seq — comprehensive multi-subset comparison; T-BET/AP-1/EGR motifs in DN2 (sources: 2)
  • RRBS — reduced-representation bisulfite sequencing; progressive hypomethylation hierarchy (sources: 1)
  • ELISpot — antigen-specific ASC quantification; DENV-specific IgG quantification; FluoroSpot for IL-21/IFN-γ in dengue (sources: 7)
  • In Vitro B Cell Stimulation — TLR7/IFN-γ/IL-21 EF differentiation; T-B coculture (sources: 3)
  • Phospho-Flow Cytometry — pERK/pMAPKp38 TLR7 readout; DN2/aNAV hyper-responsiveness (sources: 1)
  • Serum Proteomics — LC-MS/MS identification of serum antibodies from NGS databases (sources: 1)
  • Activation-Induced Marker Assay — CD25⁺OX40⁺ AIM assay for DENV-specific T cell responses (sources: 1)
  • Single-Cell RNA Sequencing — 10x Genomics scRNA-seq + scTCR-seq; Tph subcluster identification in dengue (sources: 1)
  • T-B Coculture Assay — Tph-driven memory B cell→PB differentiation; IL-21 blocking (sources: 1)
  • FRNT — focus reduction neutralization test; neutralizing titers not different by dengue severity; OAS demonstrated at mAb FRNT₅₀ level (sources: 2)
  • PRNT — plaque reduction neutralization test; PRNT₅₀ not correlated with plasmablast frequency in dengue (sources: 1)

Analyses (4)

Graph View