Immunity
Volume 47, Issue 1, 18 July 2017, Pages 118-134.e8
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Article
Human Secretory IgM Emerges from Plasma Cells Clonally Related to Gut Memory B Cells and Targets Highly Diverse Commensals

https://doi.org/10.1016/j.immuni.2017.06.013Get rights and content
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Highlights

  • IgM+ PCs generating SIgM are relatively abundant in human but not mouse gut

  • IgM+ PCs clonally relate to a large gut repertoire of memory IgM+ B cells

  • Gut memory IgM+ B cells express a tissue-specific signature and can switch to IgA

  • Human but not mouse SIgM binds a highly diverse microbiota dually coated by SIgA

Summary

Secretory 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 cell-independent or T cell-dependent signals. These signals induced abundant IgM which, together with SIgM from clonally affiliated PCs, recognized mucus-embedded commensals. Bacteria recognized by human SIgM were dually coated by SIgA and showed increased richness and diversity compared to IgA-only-coated or uncoated bacteria. Thus, SIgM may emerge from pre-existing memory rather than newly activated naive IgM+ B cells and could help SIgA to anchor highly diverse commensal communities to mucus.

Keywords

human
IgM
IgA
gut
mucosa
memory B cells
plasma cells
repertoire
microbiota

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These authors contributed equally

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