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BCR affinity differentially regulates colonization of the subepithelial dome and infiltration into germinal centers within Peyer's patches.

Journal article
Authors Adi Biram
Anneli Strömberg
Eitan Winter
Liat Stoler-Barak
Ran Salomon
Yoseph Addadi
Rony Dahan
Gur Yaari
Mats Bemark
Ziv Shulman
Published in Nature immunology
Volume 20
Issue 4
Pages 482-492
ISSN 1529-2916
Publication year 2019
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 482-492
Language en
Links dx.doi.org/10.1038/s41590-019-0325-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords IgA, Peyer´s patches, B cell activation, germinal center
Subject categories Immunobiology, Immunology in the medical area

Abstract

Gut-derived antigens trigger immunoglobulin A (IgA) immune responses that are initiated by cognate B cells in Peyer's patches (PPs). These cells colonize the subepithelial domes (SEDs) of the PPs and subsequently infiltrate pre-existing germinal centers (GCs). Here we defined the pre-GC events and the micro-anatomical site at which affinity-based B cell selection occurred in PPs. Using whole-organ imaging, we showed that the affinity of the B cell antigen receptor (BCR) regulated the infiltration of antigen-specific B cells into GCs but not clonal competition in the SED. Follicular helper-like T cells resided in the SED and promoted its B cell colonization, independently of the magnitude of BCR affinity. Imaging and immunoglobulin sequencing indicated that selective clonal expansion ensued during infiltration into GCs. Thus, in contrast to the events in draining lymph nodes and spleen, in PPs, T cells promoted mainly the population expansion of B cells without clonal selection during pre-GC events. These findings have major implications for the design of oral vaccines.

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