Human secretory IgM emerges from plasma cells clonally related to gut memory B cells and targets highly diverse commensals

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 r...

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Bibliographic Details
Authors: Magri, Giuliana; Comerma, Laura; Pybus, Marc; Sintes, Jordi; Lligé, David; Segura-Garzón, Daniel; Bascones, Sabrina; Yeste, Ada; Grasset, Emilie K.; Gutzeit, Cindy; Uzzan, Mathieu; Ramanujam, Meera; van Zelm, Menno C.; Albero González, Raquel; Vazquez, Ivonne; Iglesias, Mar; Serrano, Sergi; Márquez, Lucía; Mercadé Gil, M. Elena; Mehandru, Saurabh; Cerutti, Andrea
Format: Article
Status:Accepted version
Publication date:2017
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/168922
Online Access:https://hdl.handle.net/2445/168922
Access Level:Open access
Keyword:Cèl·lules B
Mucosa gastrointestinal
B cells
Gastrointestinal mucosa
Description
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.