Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut

Fritz, Jörg H; Rojas, Olga Lucia; Simard, Nathalie; McCarthy, Douglas D; Hapfelmeier, Siegfried; Rubino, Stephen; Robertson, Susan J; Larijani, Mani; Gosselin, Jean; Ivanov, Ivaylo I; Martin, Alberto; Casellas, Rafael; Philpott, Dana J; Girardin, Stephen E; McCoy, Kathy D; Macpherson, Andrew J; Paige, Christopher J; Gommerman, Jennifer L (2012). Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut. Nature, 481(7380), pp. 199-203. London: Macmillan Journals Ltd. 10.1038/nature10698

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The largest mucosal surface in the body is in the gastrointestinal tract, a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA (ref. 1). Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells. However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract. Here we report that mouse IgA(+) plasma cells also produce the antimicrobial mediators tumour-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA(+) plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-α and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining homeostasis in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
UniBE Contributor:	Hapfelmeier, Siegfried Hektor, McCoy, Kathleen, Macpherson, Andrew
ISSN:	0028-0836
Publisher:	Macmillan Journals Ltd.
Language:	English
Submitter:	Siegfried Hektor Hapfelmeier-Balmer
Date Deposited:	04 Oct 2013 14:22
Last Modified:	05 Dec 2022 14:06
Publisher DOI:	10.1038/nature10698
PubMed ID:	22158124
Web of Science ID:	000298981200039
URI:	https://boris.unibe.ch/id/eprint/7749 (FactScience: 213075)