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Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization

Journal article
Authors Mats Bemark
H. Hazanov
Anneli Strömberg
Rathan Komban
Joel Holmqvist
Sofia Köster
Johan Mattsson
P. Sikora
R. Mehr
Nils Y Lycke
Published in Nature Communications
Volume 7
ISSN 2041-1723
Publication year 2016
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Language en
Links dx.doi.org/10.1038/ncomms12698
Subject categories Immunology in the medical area, Immunology

Abstract

Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8high /GFP+ NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin+ CD73+ PD-L2+ CD80+ and at systemic sites mostly IgM+, while 80% are IgA+ in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7+, but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization. © 2016 The Author(s).

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