EFB Dengue Literature Review

CD38

7 min read

CD38

Overview

CD38 is a type II transmembrane glycoprotein with ectoenzyme (NAD glycohydrolase/cyclase) activity, expressed at varying levels across B cell developmental stages. In B cell immunology, it is used in combination with IgD (Bm1–Bm5 classification) or CD27 to resolve B cell subsets. Very high CD38 expression marks plasmablasts/plasma cells; intermediate expression marks GC and transitional B cells; low/negative expression marks resting memory B cells (Bm5).

Key Points from Literature

  • In the Bm1–Bm5 classification system, CD38 levels distinguish: transitional (CD38^high IgD⁺), pre-GC/Bm2ʹ (CD38⁺ IgD⁺), GC/Bm3–4 (CD38^high IgD⁻), early memory/early Bm5 (CD38^dull IgD⁻), and resting memory/Bm5 (CD38⁻ IgD⁻) (see Wei2007 - DN Memory B Cells in SLE).

  • DN B cells express CD38 at Bm5/early-Bm5 levels — parallel to conventional CD27⁺ memory cells — well below the levels of plasmablasts, transitional cells, and pre-GC cells (see Wei2007 - DN Memory B Cells in SLE).

  • In SLE, both CD27⁺ memory cells and DN cells show a shift toward the CD38^dull (early Bm5) phenotype at the expense of the CD38⁻ (Bm5) fraction seen in healthy donors (see Wei2007 - DN Memory B Cells in SLE).

  • CD38^high expression combined with IgD⁻ and CD27⁺ identifies plasmablasts/plasma cells in PBL (see Wei2007 - DN Memory B Cells in SLE).

  • Combined CD38/CD19/CD20 plasmablast gate: CD38^high, CD19^low, CD20⁻ provides the most specific plasmablast identification, distinguishing them from pre-GC (Bm2ʹ) cells which are CD38^high but CD19^bright, CD20⁺. In SLE, this gate identifies 18.5 ± 17.9% of PBL B cells vs. 0.24 ± 0.23% in controls (P=0.001; see Anolik2004 - Rituximab and B Cell Abnormalities in SLE, n=15 SLE, n=5 controls).

  • Pre-GC (Bm2ʹ) identification: CD38^high, CD19⁺, CD20⁺, CD10⁺ (IgD⁺); a distinct circulating GC founder population expanded in some SLE patients. Mean 4.7 ± 2.8% in healthy controls. These cells are resistant to rituximab-mediated depletion in some patients (see Anolik2004 - Rituximab and B Cell Abnormalities in SLE).

  • CD38^lo in acN cells: Activated naive (acN) B cells are CD38^lo — well below the CD38^hi level that marks plasmablasts, transitional B cells, and GC cells. This low-CD38 expression, combined with CD19^hi, CD21⁻, CD23⁻, IgM^lo, and CD24⁻, helps distinguish acN cells from other CD38-expressing populations (see Tipton2015 - ASC Diversity and Origin in SLE).

  • Full ASC gate (Tipton2015): CD19⁺IgD⁻CD27^hiCD38^hi identifies ASCs as used in Tipton2015, with subsequent CD138⁻/CD138⁺ sub-gating for maturation staging. This is a standardised Sanz lab gate consistent across Wei2007 and Anolik2004 publications.

  • CD38⁻ defines DN2 cells: DN2 B cells (IgD⁻CD27⁻CXCR5⁻CD21⁻CD11c⁺) are CD38⁻, placing them at the same level as resting Bm5 memory cells and clearly below the CD38^hi plasmablast gate. This CD38⁻ phenotype is shared with aNAV cells and is consistent with the broader pattern that the EF differentiation pathway (rNAV → aNAV → DN2 → plasmablast) only acquires CD38^hi expression at the terminal plasmablast stage (see Jenks2018 - DN2 B Cells and EF Pathway in SLE, flow cytometry).

  • CD38^high in the first dengue plasmablast gate: Wrammert2012 used CD38^high combined with CD27^high as the defining plasmablast markers (within CD19⁺CD3⁻CD20⁻/low), identifying cells that averaged 47% of CD19⁺ B cells in acute dengue. This gate is the simplest dengue application (5-color) and confirms that CD38^high is the most consistent plasmablast marker across all dengue studies in this wiki (see Wrammert2012 - Plasmablast Responses in Acute Dengue, 5-color conventional FCM).

  • CD38^hi used in PB sorting panel with CD138 in dengue clonal study: Appanna2016 included both CD38 and CD138 in the PB sorting panel (CD19⁺CD20⁻CD27^hiCD38^hi), with CD138 as a fifth marker. CD38^hi remains the core PB identifier consistent across all dengue studies in the wiki (see Appanna2016 - Plasmablasts as Subset of Memory B Cell Pool, FACSAria, n=12 dengue).

  • CD38 is core marker (5) and does triple duty in this scheme. It anchors the second of the two recommended schemes (IgD vs CD38 = Bm1–Bm5); paired with CD24 it resolves five fractions separating naive from memory and from transitional; and paired with CD138 on IgD⁻ cells it splits ASC into five populations (Pop1 CD19⁺CD38ᵐⁱᵈCD138⁻ through Pop5 CD19⁻CD38ʰⁱCD138⁺). In Table 1 it is one of the three co-varying axes separating DN1 (CD38⁺CD24⁺CD21⁺) from DN2 (CD38⁻CD24⁻CD21⁻), and CD38ʰⁱ with IgD⁺ marks transitional cells that a CD21-anchored activation gate would otherwise capture (see Sanz2019 - Consistent Classification of Human B Cell Populations, review — no original data).

  • [2026-08-29] CD38 does double duty on the Emory lupus panel, at both ends of the tree. High CD38 with high CD27 (IgD⁻CD27⁺⁺CD38⁺⁺) defines plasmablasts; high CD38 with high CD24 (CD24^hi CD38^hi) defines the transitional T1+T2 population inside the naive+transitional gate. Both were used in a 207-patient lupus-spectrum cohort with 46 healthy controls, on cryopreserved PBMC (see Jenks2021 - B Cell Subset Composition in Cutaneous Lupus, cross-sectional, conventional flow).

  • CD38^hi^ with CD27⁺ is this study’s ASC definition, and the readout for every differentiation experiment. ASCs were enumerated throughout as CD38^hi^CD27⁺, including the head-to-head assay in which sorted SLE T-bet^hi^ DN2 cells yielded ≥50-fold more ASCs than naive B cells after only 2.5 days (see Zumaquero2019 - IFN-gamma Programs T-bet-hi B Cells for ASC Differentiation, human, n=20 HD + n=40 SLE + in vitro reconstruction). Note the contrast with the mouse convention used by the same laboratory — Stone2019 - T-bet Promotes ASC Differentiation by Limiting IFN-gamma Inflammation gates mouse ASC as CD138⁺CD93⁺ — the two marker sets are not interchangeable.

  • CD38⁺⁺ scores de novo plasmablast generation in vitro, not only ex vivo classification. The CD27⁺⁺CD38⁺⁺ gate was taken over unchanged from Wrammert2012 - Plasmablast Responses in Acute Dengue and used as the endpoint of a 6-day coculture: CD38⁺⁺ cells reached 22.8% of total B cells with DENV-infected monocytes, 5.21% with monocyte-derived DCs and 3.83% with B cells alone, arising predominantly within the CFSE-diluted proliferating fraction (see Kwissa2014 - Monocytes Drive Plasmablast Differentiation in Dengue, in vitro, 4 independent experiments with 4 healthy blood donors). Worth reading against the CD38⁻ DN2 entry above: in this system the CD38⁺⁺ step is the terminal one and is reached from resting B cells within six days without any T cell help. The paper contributes no new evidence on CD38 biology itself.

  • In mouse, CD38 retention alongside absent CD138 is what makes the T-bet⁺CD11c⁺ population memory-like rather than secretory. Surface staining at days 10, 12 and 15 p.i. showed increased CD38 but not CD138, which the authors read as a phenotype resembling “memory B cells and not PCs”; the IgD^lo^CD38⁺GL-7⁻ memory phenotype persisted to at least day 35 (see Song2022 - Tfh Outside Germinal Centers Drive T-bet CD11c B Cells, mouse, LCMV-Armstrong, n=3–5 mice/group). ⚠ Wiki caution, not a claim of this source: the murine CD38 polarity used here (high on memory, low on plasma cells) is the inverse of the human CD38^hi^CD27^hi^ plasmablast gate this page otherwise describes — the gate does not transfer between species.

Contradictions & Debates

None documented in current wiki sources.

Double-Negative B Cell, DN2 B Cell, Activated Naive B Cell, Memory B Cell, Plasmablast, CD138, IgD, CD27, Conventional Flow Cytometry

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