2017
DOI: 10.1016/j.immuni.2017.06.013
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Human Secretory IgM Emerges from Plasma Cells Clonally Related to Gut Memory B Cells and Targets Highly Diverse Commensals

Abstract: SummarySecretory immunoglobulin A (SIgA) enhances host-microbiota symbiosis, whereas SIgM remains poorly understood. We found that gut IgM+ plasma cells (PCs) were more abundant in humans than mice and clonally related to a large repertoire of memory IgM+ B cells disseminated throughout the intestine but rare in systemic lymphoid organs. In addition to sharing a gut-specific gene signature with memory IgA+ B cells, memory IgM+ B cells were related to some IgA+ clonotypes and switched to IgA in response to T ce… Show more

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Cited by 166 publications
(183 citation statements)
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“…As we delve into these subsets, it is now clear that a lack of terminal differentiation endows cells with enhanced plasticity. For example, our work and the work of others have demonstrated that IgM + MBCs can rapidly class switch to IgG‐expressing plasmablasts, whereas work from Cerutti and colleagues has demonstrated that IgM + MBCs can also switch to IgA‐expressing plasmablasts . Whether these IgM precursors are related or not is an open question.…”
Section: Discussionmentioning
confidence: 80%
“…As we delve into these subsets, it is now clear that a lack of terminal differentiation endows cells with enhanced plasticity. For example, our work and the work of others have demonstrated that IgM + MBCs can rapidly class switch to IgG‐expressing plasmablasts, whereas work from Cerutti and colleagues has demonstrated that IgM + MBCs can also switch to IgA‐expressing plasmablasts . Whether these IgM precursors are related or not is an open question.…”
Section: Discussionmentioning
confidence: 80%
“…This observation, together with the recent characterization of dually coated (IgA + IgM + ) mucus-embedded bacteria with increased richness compared to IgA-only-coated bacteria (52), suggests that IgM may compensate IgA deficiency. We show that microbial IgM binding is highly variable between patients.…”
Section: Of 15mentioning
confidence: 81%
“…In mouse, B1 cells serve as the major source for polyclonal low‐affinity anti‐commensal IgM responses as a primitive natural antibody response . However, in contrast to mice, humans have more abundant IgM + plasma cells in the gut, which secrete IgM antibodies that help retain a diverse community of commensals in the mucus layer in synergy with IgA . Surprisingly, a considerable amount of IgG2b and IgG3 has been identified in the secretory compartment in the gut as well.…”
Section: B‐cell–gut Microbiota Interactionsmentioning
confidence: 99%