EFB Dengue Literature Review

IgA

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IgA

Overview

IgA is the predominant immunoglobulin isotype at mucosal surfaces. In peripheral blood, IgA⁺ B cells represent a minor switched memory fraction. Like IgG, surface IgA expression marks cells that have undergone class switch recombination.

Key Points from Literature

  • DN (IgD⁻CD27⁻) B cells contain an IgA⁺ fraction in addition to IgG⁺ and IgM⁺ subsets — demonstrated in SLE patients (see Wei2007 - DN Memory B Cells in SLE, Fig. 8). The proportion of IgA⁺ cells within the DN compartment was not quantified numerically in the paper.

  • The presence of IgA⁺ cells in the DN compartment confirms that CD40-independent class switching (via BLyS/APRIL or other EF mechanisms) can produce IgA as well as IgG in extrafollicular settings (see Wei2007 - DN Memory B Cells in SLE).

  • IgA minor component of dengue plasmablast response: DENV-specific IgA-secreting plasmablasts were detectable in most patients but at ~100-fold lower frequency than IgG-secreting cells. This establishes IgA as a consistent but quantitatively minor isotype in the acute dengue plasmablast wave (see Wrammert2012 - Plasmablast Responses in Acute Dengue, ELISpot, n=46).

  • IgA sequences are present in circulating ASCs during SLE flares and vaccination responses, as part of the IgG + IgA switched isotype pool that constitutes the majority of ASC sequences in peripheral blood (see Tipton2015 - ASC Diversity and Origin in SLE, NGS isotype analysis).

  • IgA detected as a minor component in dengue PB and MBC BCR repertoires: In 454 sequencing of sorted plasmablast and MBC pools, IgA sequences were present alongside IgG and IgM. The isotype distribution showed IgG dominance in plasmablasts and non-DENV-binding MBCs, with IgM enrichment in DENV-binding MBCs. IgA contributed a minor fraction across all compartments (see Appanna2016 - Plasmablasts as Subset of Memory B Cell Pool, 454 sequencing, n=4 patients).

  • IgA is one of the two dominant switched isotypes of the ABC population. The majority of ABCs are class-switched, predominantly expressing IgG or IgA — confirming that the EF/atypical class-switching machinery produces IgA as well as IgG (consistent with the IgA⁺ fraction in the DN compartment) (see Lamprinou2026 - ABCs and DN B Cells, opinion, citing Ambegaonkar 2022; independently stated in Glaros2025 - Multilayered Identity of B Cell Memory, review).

  • ★ IgA dominates the lung resident-memory compartment, and only mucosal immunization induces it. After respiratory infection the B resident memory (BRM) pool is predominantly IgA⁺, with a smaller IgG⁺ fraction. IgG⁺ memory distributes across both lung and mediastinal lymph nodes, whereas IgA⁺ memory localizes primarily within the lung parenchyma, spatially associated with IgA-secreting plasma cells and inducible bronchus-associated lymphoid tissue (iBALT). Critically, systemic immunization fails to induce lung IgA⁺ memory, while intranasal immunization induces it effectively (see Glaros2025 - Multilayered Identity of B Cell Memory, review, no original data, mouse + human). See Tissue-Resident Memory B Cell.

  • Gut IgA⁺ memory is long-lived, clonally linked to lamina propria plasma cells, and substantially early-life in origin. IgA⁺ MBCs persist in Peyer’s patches and mesenteric lymph nodes more than a year after priming, are clonally related to lamina propria plasma cells, and contribute to replenishing that PC pool after depletion. A large share of both IgA⁺ PCs in the small intestinal lamina propria and bone marrow, and a significant fraction of GC-derived MBCs in Peyer’s patches, derive from B cell clones generated within the first two weeks of life (see Glaros2025 - Multilayered Identity of B Cell Memory, review, mouse lineage tracing).

  • IgA appears in Table 1 only as part of the undifferentiated “IgM/IgG/IgA⁺” annotation on the DN1 and DN2 rows — the third, FcRL4⁺ DN row carries no isotype annotation at all — and IgA is classed as an additional rather than a core marker. The review offers no IgA-specific claim about the DN or atypical compartment — recorded here so the absence is on the record rather than inferred (see Sanz2019 - Consistent Classification of Human B Cell Populations, review — no original data).

  • A measured negative: monocyte-driven differentiation raises IgG and IgM but not IgA. DENV-infected monocytes stimulated “secretion of IgG and IgM (but not IgA) to a level significantly higher than that of MDDCs or controls” in a 6-day coculture with resting allogeneic CD19⁺ B cells; IgA titres were assayed on day 6 in the same wells, so this is a measured negative rather than an unreported isotype (see Kwissa2014 - Monocytes Drive Plasmablast Differentiation in Dengue, in vitro, 4 independent experiments with 4 healthy blood donors). Consistent in direction with IgA being a quantitatively minor output of the acute dengue plasmablast wave in vivo (~100-fold below IgG, Wrammert2012 - Plasmablast Responses in Acute Dengue). Scope limit: the only added signals were IL-2, CpG and the infected monocyte — the study tested no IgA-inducing condition, so this is a negative for that condition and not a statement about IgA switching capacity.

Contradictions & Debates

None documented in current wiki sources.

Double-Negative B Cell, Age-Associated B Cell, IgG, IgM, Class Switch Recombination, Tissue-Resident Memory B Cell, Early Memory B Cell

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