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.

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European Nucleotide Archive

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Acknowledgements

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).

Author information

Author notes

    • Cornelia Lindner
    •  & Irene Thomsen

    These authors contributed equally to this work.

Affiliations

  1. Institute of Immunology, Hannover Medical School, Hannover, Germany.

    • Cornelia Lindner
    • , Irene Thomsen
    • , Benjamin Wahl
    • , Milas Ugur
    • , Maya K Sethi
    • , Michaela Friedrichsen
    •  & Oliver Pabst
  2. Laboratory for Animal Science, Hannover Medical School, Hannover, Germany.

    • Anna Smoczek
    •  & André Bleich
  3. Department for Internal Medicine I, University Hospital Schleswig Holstein, Kiel, Germany.

    • Stephan Ott
    •  & Stefan Schreiber
  4. Pediatric Gastroenterology, Hannover Medical School, Hannover, Germany.

    • Ulrich Baumann
  5. Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.

    • Sebastian Suerbaum
  6. Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany.

    • Stefan Schreiber
    •  & Philip Rosenstiel
  7. INSERM UMR1163, Laboratory of Intestinal Immunity, Institut Imagine, Paris, France.

    • Valérie Gaboriau-Routhiau
    •  & Nadine Cerf-Bensussan
  8. The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.

    • Helena Hazanov
    •  & Ramit Mehr
  9. Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.

    • Preben Boysen
  10. Institute of Molecular Medicine, RWTH Aachen, Aachen, Germany.

    • Oliver Pabst

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Contributions

C.L. and I.T. performed experiments and analyzed data; M.U. performed cell-tracking experiments; B.W. generated tools for data analysis; M.F., M.K.S. and S. Suerbaum supported sequencing experiments; A.B. and A.S. performed colonization experiments; V.G.-R. and N.C.-B. provided samples from monocolonized mice; H.H. and R.M. helped with sequencing data analysis; P.B. performed cohousing experiments; S.O., U.B., S. Schreiber and P.R. provided human samples; and O.P. performed mouse surgery, designed the study and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Oliver Pabst.

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DOI

https://doi.org/10.1038/ni.3213

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