EFB Dengue Literature Review

IgM

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IgM

Overview

IgM is the first immunoglobulin isotype produced by B cells and the default surface isotype on mature naive B cells (co-expressed with IgD). Secreted IgM is a pentamer and mediates efficient complement activation. IgM⁺ memory B cells (retaining surface IgM without isotype switching) represent a distinct memory subset; whether they originate from GC or GC-independent pathways is debated.

Key Points from Literature

  • ~15% of DN (IgD⁻CD27⁻) B cells in healthy subjects are IgM⁺ (surface IgM without IgD); similar proportion in SLE. Crucially, these IgM⁺DN cells lack IgD, distinguishing them from conventional unswitched CD27⁺ memory cells (IgM⁺IgD⁺) (see Wei2007 - DN Memory B Cells in SLE, n=29 healthy cross-sectional).

  • IgM⁺IgD⁺ CD27⁺ memory cells (conventional unswitched memory) are proposed to represent recirculating marginal zone B cells; IgM-only CD27⁺ memory cells may represent precursors to isotype-switched cells in the context of hyper-IgM syndrome. The IgM⁺ DN cells do not fit cleanly into either model (see Wei2007 - DN Memory B Cells in SLE).

  • IgM contribution to SLE ASC sequences: IgM accounts for 5.42–19.53% of all sequences in circulating ASCs from SLE patients (substantial inter-subject variability). The frequency of IgM sequences in the IgD⁻CD27⁺ memory compartment is significantly greater in SLE (20.9–68.1%) vs. vaccinated healthy controls (1.5–37.5%; p<0.05), consistent with active generation of IgM-only memory from recently activated naive cells — the first GC-independent memory layer (see Tipton2015 - ASC Diversity and Origin in SLE, NGS of sorted populations, n=5 SLE, n=8 vaccinated).

  • IgM⁻ memory cells as indicator of acN cell contribution: The high IgM fraction in SLE memory is attributed to naive cell recruitment — newly activated B cells produce IgM-only memory before undergoing class switch recombination, consistent with the acN → EF pathway (see Tipton2015 - ASC Diversity and Origin in SLE, citing Dogan et al. 2009).

  • IgM near-absent in secondary dengue plasmablast wave: In a predominantly secondary dengue cohort (42/46), IgM-secreting DENV-specific plasmablasts were detectable in only a minority of patients and were never IgM-only — all had concurrent IgG responses. The 4 primary responders all had detectable IgM by ELISpot, with one (Den01-066) showing an IgM response exceeding IgG. This confirms that the secondary dengue plasmablast response is overwhelmingly class-switched, with IgM production restricted to primary infection (see Wrammert2012 - Plasmablast Responses in Acute Dengue, ELISpot, n=46).

  • IgM⁺ DENV-binding MBCs dominate the virus-specific memory compartment and harbour the only PB-shared clones: In Appanna2016, a large fraction of DENV-binding convalescent MBCs expressed IgM (vs. IgG-dominant plasmablasts and IgG-dominant non-DENV-binding MBCs). The rare CDR3 sequences shared between PBs and DENV-binding MBCs were exclusively IgM, and shared clones that were expanded in the MBC compartment were also IgM. The authors interpret this as potential enrichment of low-affinity IgM binders during virus-based sorting (DENV binding was also observed in non-immune individuals). This connects to the Singh2026 finding that IgM⁺ DENV-specific MBCs are the only subset significantly elevated during acute secondary dengue (see Appanna2016 - Plasmablasts as Subset of Memory B Cell Pool, 454 + Sanger sequencing, n=12 dengue).

Contradictions & Debates

None documented in current wiki sources.

Double-Negative B Cell, Memory B Cell, Activated Naive B Cell, IgD, IgG, Class Switch Recombination

Sources

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