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

Adi Biram, Anneli Strömberg, Eitan Winter, Liat Stoler-Barak, Ran Salomon, Yoseph Addadi, Rony Dahan, Gur Yaari, Mats Bemark, Ziv Shulman

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish
Pages (from-to)482-492
Number of pages11
JournalNature Immunology
Issue number4
StatePublished - 1 Apr 2019

Bibliographical note

Funding Information:
Z.S. is supported by the European Research Council (grant No. 677713), Human Frontiers of Science Program (grant No. CDA-00023/2016), Israel Science Foundation (grant No. 1090/18), Azrieli Foundation, Rising Tide Foundation and the Morris Kahn Institute for Human Immunology. Z.S. is a member in the European Molecular Biology Organization Young Investigator Program and is supported by grants from The Benoziyo Endowment Fund for the Advancement of Science, The Sir Charles Clore Research Prize, Comisaroff Family Trust, Irma & Jacques Ber-Lehmsdorf Foundation, Gerald O. Mann Charitable Foundation and David M. Polen Charitable Trust. Imaging was made possible thanks to The de Picciotto-Lesser Cell Observatory in memory of Wolf and Ruth Lesser.

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.


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