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

• Published in: Immunity (Cambridge, Mass.) Mass.), 2017-07, Vol.47 (1), p.118-134.e8
• Main 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, Mercade, Elena, Mehandru, Saurabh, Cerutti, Andrea
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Angiodysplasia - immunology; Animals; Antigens; B-Lymphocytes - immunology; Bacteria; Bioinformatics; Clone Cells; Colonic Neoplasms - immunology; Colonic Polyps - immunology; Commensals; Digestive system; Female; Flow cytometry; Gastrointestinal Microbiome - immunology; Gastrointestinal tract; gut; Homeostasis; human; Humans; IgA; IgM; Immune system; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin A - metabolism; Immunoglobulin Class Switching; Immunoglobulin M; Immunoglobulin M - metabolism; Immunoglobulins; Immunologic Memory; Immunological memory; Intestine; Intestines - immunology; Intestines - microbiology; Lymphocyte receptors; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; memory B cells; Memory cells; Mice; Mice, Inbred C57BL; microbiota; Middle Aged; Mouse devices; mucosa; Mucus; Organs; Plasma cells; Plasma Cells - immunology; Production increases; repertoire; Small intestine; Symbiosis
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2017.06.013

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. [Display omitted] •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 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.