Maturation of the Human Immunoglobulin Heavy Chain Repertoire With Age

Frontiers in Immunology

卷:11

Dominic F. Kelly¹  Jacob D. Galson²  Valentin von Niederhäusern³  Marie Ghraichy³  Jana Pachlopnik Schmid³  Johannes Trück³  Aleksandr Kovaltsuk⁴  Charlotte M. Deane⁴  Mike Recher⁶  Annaïse J. Jauch⁶  Enkelejda Miho¹⁰ 

[1] 0Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom;

[2] Alchemab Therapeutics Ltd, London, United Kingdom;

[3] Children's Research Center, University of Zurich, Zurich, Switzerland;

[4] Department of Statistics, University of Oxford, Oxford, United Kingdom;

[5] Division of Immunology, University Children's Hospital, University of Zurich, Zurich, Switzerland;

[6] Immunodeficiency Laboratory, Department of Biomedicine, University and University Hospital of Basel, Basel, Switzerland;

[7] Institute of Medical Engineering and Medical Informatics, University of Applied Sciences and Arts Northwestern Switzerland FHNW, Muttenz, Switzerland;

[8] Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom;

[9] SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland;

[10] aiNET GmbH, Basel, Switzerland;

关键词: antibody;    B cells;    children;    heavy chain;    immunoglobulin;    maturation;   

DOI  :  10.3389/fimmu.2020.01734

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown