EFB Dengue Literature Review

CD38

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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).

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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