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Maturation of the Human B-Cell Receptor Repertoire with Age

26 Pages Posted: 15 Jan 2020 Sneak Peek Status: Under Review

See all articles by Marie Ghraichy

Marie Ghraichy

University of Zurich - Division of Immunology

Jacob D. Galson

University of Zurich - Children's Research Center

Aleksandr Kovaltsuk

University of Oxford - Department of Statistics

Valentin von Niederhäusern

University of Zurich - Division of Immunology

Jana Pachlopnik Schmid

University of Zurich - Division of Immunology

Mike Recher

University of Basel - Immunodeficiency Laboratory

Annaïse J. Jauch

University of Basel - Immunodeficiency Laboratory

Enkelejda Miho

University of Applied Sciences and Arts, Northwestern Switzerland - Institute of Medical Engineering and Medical Informatics

Dominic F. Kelly

University of Oxford - Oxford Vaccine Group

Charlotte M. Deane

University of Oxford - Department of Statistics

Johannes Trück

University of Zurich - Division of Immunology

More...

Abstract

B cells play a central role in adaptive immune processes, mainly through the production of antibodies. The maturation of the B-cell system with age is poorly studied. We extensively investigated age-related alterations of naïve and antigen-experienced B-cell receptor (BCR) repertoires. The most significant changes were observed in the first 10 years of life, and were characterized by altered immunoglobulin gene usage and an increased frequency of mutated antibodies structurally diverging from their germline precursors. Older age was associated with an increased usage of downstream constant region genes and fewer antibodies with self-reactive properties. As mutations accumulated with age, the frequency of germline-encoded self-reactive antibodies decreased, indicating a possible beneficial role of self-reactive B-cells in the developing immune system. Our results suggest a continuous process of change through childhood across a broad range of parameters characterizing BCR repertoires and stress the importance of using well-selected, age-appropriate controls in BCR studies.

Keywords: antibody, B cells, B-cell receptor, children, Maturation, repertoire

Suggested Citation

Ghraichy, Marie and Galson, Jacob D. and Kovaltsuk, Aleksandr and von Niederhäusern, Valentin and Schmid, Jana Pachlopnik and Recher, Mike and Jauch, Annaïse J. and Miho, Enkelejda and Kelly, Dominic F. and Deane, Charlotte M. and Trück, Johannes, Maturation of the Human B-Cell Receptor Repertoire with Age. ISCIENCE-D-20-00027. Available at SSRN: https://ssrn.com/abstract=3518535 or http://dx.doi.org/10.2139/ssrn.3518535
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Marie Ghraichy

University of Zurich - Division of Immunology

Switzerland

Jacob D. Galson

University of Zurich - Children's Research Center

Switzerland

Aleksandr Kovaltsuk

University of Oxford - Department of Statistics

24-29 St Giles
Oxford
United Kingdom

Valentin Von Niederhäusern

University of Zurich - Division of Immunology

Switzerland

Jana Pachlopnik Schmid

University of Zurich - Division of Immunology

Switzerland

Mike Recher

University of Basel - Immunodeficiency Laboratory

Switzerland

Annaïse J. Jauch

University of Basel - Immunodeficiency Laboratory

Switzerland

Enkelejda Miho

University of Applied Sciences and Arts, Northwestern Switzerland - Institute of Medical Engineering and Medical Informatics

Switzerland

Dominic F. Kelly

University of Oxford - Oxford Vaccine Group

United Kingdom

Charlotte M. Deane

University of Oxford - Department of Statistics

24-29 St Giles
Oxford
United Kingdom

Johannes Trück (Contact Author)

University of Zurich - Division of Immunology ( email )

Switzerland

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