Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota

Cornelia Lindner, Irene Thomsen, Benjamin Wahl, Milas Ugur, Maya K. Sethi, Michaela Friedrichsen, Anna Smoczek, Stephan Ott, Ulrich Baumann, Sebastian Suerbaum, Stefan Schreiber, André Bleich, Valérie Gaboriau-Routhiau, Nadine Cerf-Bensussan, Helena Hazanov, Ramit Mehr, Preben Boysen, Philip Rosenstiel, Oliver Pabst

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

Secretory immunoglobulin A (SIgA) shields the gut epithelium from luminal antigens and contributes to host-microbe symbiosis. However, how antibody responses are regulated to achieve sustained host-microbe interactions is unknown. We found that mice and humans exhibited longitudinal persistence of clonally related B cells in the IgA repertoire despite major changes in the microbiota during antibiotic treatment or infection. Memory B cells recirculated between inductive compartments and were clonally related to plasma cells in gut and mammary glands. Our findings suggest that continuous diversification of memory B cells constitutes a central process for establishing symbiotic host-microbe interactions and offer an explanation of how maternal antibodies are optimized throughout life to protect the newborn.

Original languageEnglish
Pages (from-to)880-888
Number of pages9
JournalNature Immunology
Volume16
Issue number8
DOIs
StatePublished - Aug 2015

Bibliographical note

Publisher Copyright:
© 2015, Nature Publishing Group. All rights reserved.

Funding

We thank U. Kalinke (TWINCORE, Hannover, Germany), A. Krueger, I. Prinz, O. Schulz, S. Woltemate (Hannover Medical School, Hannover, Germany), M. Bemark (University of Gothenburg, Gothenburg, Sweden), B. Wabakken Hognestad and D. Ölsner (both at the Norwegian University of Life Sciences, Oslo, Norway), and R. Bharti (IKMB, University of Kiel, Kiel, Germany). This work was supported by the DFG Cluster of Excellence Inflammation at Interfaces (CL VIII to P.R., S.O. and S. Schreiber), the BMBF (grant SysINFLAME (TP3/4) to P.R.), the Israel Science Foundation (grant 270/09 to R.M.), the German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig and Deutsche Forschungsgemeinschaft (grants PA921/4-1 (to O.P.) and SFB621-Z).

FundersFunder number
DFG Cluster of Excellence Inflammation at Interfaces
German Centre for Infection Research
Deutsches Zentrum für Infektionsforschung
Deutsche ForschungsgemeinschaftSFB621-Z, PA921/4-1
Bundesministerium für Bildung und ForschungTP3/4
Israel Science Foundation270/09

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