Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine

Lindner, Cornelia; Wahl, Benjamin; Föhse, Lisa; Suerbaum, Sebastian; Macpherson, Andrew J; Prinz, Immo; Pabst, Oliver (2012). Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine. Journal of experimental medicine, 209(2), pp. 365-77. New York, N.Y.: Rockefeller University Press 10.1084/jem.20111980

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Intestinal immunoglobulin A (IgA) ensures host defense and symbiosis with our commensal microbiota. Yet previous studies hint at a surprisingly low diversity of intestinal IgA, and it is unknown to what extent the diverse Ig arsenal generated by somatic recombination and diversification is actually used. In this study, we analyze more than one million mouse IgA sequences to describe the shaping of the intestinal IgA repertoire, its determinants, and stability over time. We show that expanded and infrequent clones combine to form highly diverse polyclonal IgA repertoires with very little overlap between individual mice. Selective homing allows expanded clones to evenly seed the small but not large intestine. Repertoire diversity increases during aging in a dual process. On the one hand, microbiota-, T cell-, and transcription factor RORγt-dependent but Peyer's patch-independent somatic mutations drive the diversification of expanded clones, and on the other hand, new clones are introduced into the repertoire of aged mice. An individual's IgA repertoire is stable and recalled after plasma cell depletion, which is indicative of functional memory. These data provide a conceptual framework to understand the dynamic changes in the IgA repertoires to match environmental and intrinsic stimuli.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology

UniBE Contributor:

Macpherson, Andrew

ISSN:

0022-1007

Publisher:

Rockefeller University Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:40

Last Modified:

17 Mar 2015 21:34

Publisher DOI:

10.1084/jem.20111980

PubMed ID:

22249449

Web of Science ID:

000301943200015

URI:

https://boris.unibe.ch/id/eprint/16156 (FactScience: 223743)

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