Maturation of the human immunoglobulin heavy chain repertoire with age

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 immunoglobulin heavy chain (IgH) 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 IgH 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 IgH repertoires and stress the importance of using well-selected, age-appropriate controls in IgH studies.

Keywords

Antibody, B cells, Children, Heavy chain, Immunoglobulin, Maturation, Repertoire, High-throughput sequencing

Subject (DDC)

610 - Medizin und Gesundheit

Project

Event

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Conference start date

Conference end date

Date of the last check

ISBN

ISSN

1664-3224

Language

English

Created during FHNW affiliation

Yes

Strategic action fields FHNW

Publication status

Published

Review

Peer review of the complete publication

Open access category

Gold

License

Citation

Ghraichy, M., Galson, J. D., Kovaltsuk, A., von Niederhäusern, V., Pachlopnik Schmid, J., Recher, M., Jauch, A. J., Miho, E., Kelly, D. F., Deane, C. M., & Trück, J. (2020). Maturation of the human immunoglobulin heavy chain repertoire with age. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.01734

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