Ageing of the B-cell repertoire

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences Vol. 370; no. 1676; p. 20140237
• Main Authors: Martin, Victoria, Wu, Yu-Chang (Bryan), Kipling, David, Dunn-Walters, Deborah
• Format: Journal Article
• Language: English
• Published: England The Royal Society 05.09.2015
• Subjects: Adult; Aged; Aged, 80 and over; Ageing; Aging - immunology; B-Cell Memory; B-Lymphocyte Subsets - immunology; Clonal Selection, Antigen-Mediated; Humans; Immunoglobulin Class Switching; Immunoglobulin Repertoire; Immunoglobulins - genetics; Immunologic Memory; Middle Aged; Subclass Of Antibody; V(D)J Recombination; Young Adult; B-cell memory; subclass of antibody; ageing; immunoglobulin repertoire
• ISSN: 0962-8436; 1471-2970; 1471-2970
• DOI: 10.1098/rstb.2014.0237

Older people are more susceptible to infection, less responsive to vaccination and have a more inflammatory immune environment. Using spectratype analysis, we have previously shown that the B-cell repertoire of older people shows evidence of inappropriate clonal expansions in the absence of challenge, and that this loss of B-cell diversity correlates with poor health. Studies on response to vaccination, using both spectratyping and high-throughput sequencing of the repertoire, indicate that older responses to challenge are lacking in magnitude and/or delayed significantly. Also that some of the biologically significant differences may be in different classes of antibody. We have also previously shown that normal young B-cell repertoires can vary between different phenotypic subsets of B cells. In this paper, we present an analysis of immunoglobulin repertoire in different subclasses of antibody in five different populations of B cell, and show how the repertoire in these different groups changes with age. Although some age-related repertoire differences occur in naive cells, before exogenous antigen exposure, we see indications that there is a general dysregulation of the selective forces that shape memory B-cell populations in older people.