Human secretory IgM emerges from plasma cells clonally related to gut memory B cells and targets highly diverse commensals
Magri, Giuliana (Institut Municipal d'Investigació Mèdica (Barcelona, Catalunya))
Comerma, Laura (Institut Municipal d'Investigació Mèdica (Barcelona, Catalunya))
Pybus, Marc (Institut Municipal d'Investigació Mèdica (Barcelona, Catalunya))
Sintes, Jordi (Institut Municipal d'Investigació Mèdica (Barcelona, Catalunya))
Llige, David (Institut Municipal d'Investigació Mèdica (Barcelona, Catalunya))
Segura Garzón, Daniel (Institut Municipal d'Investigació Mèdica (Barcelona, Catalunya))
Bascones, Sabrina (Institut Municipal d'Investigació Mèdica (Barcelona, Catalunya))
Yeste, Ada (Institut Municipal d'Investigació Mèdica (Barcelona, Catalunya))
Grasset, Emilie K. (Karolinska University Hospital and Karolinska Institutet (Suècia))
Gutzeit, Cindy (ICAHN School of Medicine at Mount Sinai. Department of Medicine)
Uzzan, Mathieu (ICAHN School of Medicine at Mount Sinai. Department of Medicine)
Ramanujam, Meera (Boehringer Ingelheim Pharmaceuticals. Immunology and Respiratory Disease Research)
Van Zelm, Menno C. (Monash University and Alfred Hospital. Department of Immunology and Pathology)
Albero González, Raquel (Hospital del Mar (Barcelona, Catalunya))
Vázquez, Ivonne (Hospital del Mar (Barcelona, Catalunya))
Iglesias, Mar (Universitat Autònoma de Barcelona)
Serrano, Sergi (Universitat Autònoma de Barcelona)
Márquez, Lucía (Hospital del Mar (Barcelona, Catalunya))
Mercadé, Elena (Universitat de Barcelona. Departament de Biologia)
Mehandru, Saurabh (ICAHN School of Medicine at Mount Sinai. Department of Medicine)
Cerutti, Andrea (Institució Catalana de Recerca i Estudis Avançats)

Date:	2017
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.
Grants:	Ministerio de Economía y Competitividad SAF2014-52483-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-832
Note:	Altres ajuts: European Research Council grant no. ERC-2011-ADG-20110310
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Human ; IgM ; IgA ; Gut ; Mucosa ; Memory B cells ; Plasma cells ; Repertoire ; Microbiota
Published in:	Immunity, Vol. 47, issue 1 (July 2017) , p. 118-134, ISSN 1097-4180

DOI: 10.1016/j.immuni.2017.06.013
PMID: 28709802

26 p, 8.4 MB

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