Human Secretory IgM Emerges from Plasma Cells Clonally Related to Gut Memory B Cells and Targets Highly Diverse Commensals

Giuliana Magri, Laura Comerma, Marc Pybus, Jordi Sintes, David Lligé, Daniel Segura-Garzón, Sabrina Bascones, Ada Yeste, Emilie K. Grasset, Cindy Gutzeit, Mathieu Uzzan, Meera Ramanujam, Menno C. van Zelm, Raquel Albero-González, Ivonne Vazquez, Mar Iglesias, Sergi Serrano, Lucía Márquez, Elena Mercade, Saurabh MehandruAndrea Cerutti

Research output: Contribution to journalArticleResearchpeer-review

68 Citations (Scopus)

Abstract

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. Magri et al. found that the human gut includes a large memory IgM+ B cell repertoire clonally related to plasma cells mounting SIgM responses against mucus-embedded commensals co-targeted by SIgA. Dually coated bacteria are detected in humans but not mice and show increased diversity and richness compared to SIgA-only-coated or uncoated bacteria.

Original languageEnglish
Pages (from-to)118-134
Number of pages17
JournalImmunity
Volume47
Issue number1
DOIs
Publication statusPublished - 18 Jul 2017

Keywords

  • Gut
  • Human
  • IgA
  • IgM
  • Memory B cells
  • Microbiota
  • Mucosa
  • Plasma cells
  • Repertoire

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