Ageing of the B-cell repertoire

Philosophical Transactions of the Royal Society B: Biological Sciences - Tập 370 Số 1676 - Trang 20140237 - 2015
Victoria Martin1, Bryan Wu2, David Kipling3, Deborah K. Dunn‐Walters1
1Division of Infection, Immunity and Inflammatory Disease, King's College London Faculty of Life Sciences & Medicine, Guys Campus, London, UK
2Randall Division of Cell and Molecular Biophysics, King's College London Faculty of Life Sciences & Medicine, Guys Campus, London, UK
3Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, UK

Tóm tắt

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.

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Tài liệu tham khảo

10.3389/fimmu.2011.00081

10.1182/blood-2010-03-275859

10.3324/haematol.2009.011049

10.1007/BF03401921

10.1038/leu.2009.186

10.1186/ar627

10.1016/j.leukres.2009.05.008

Shin E, 1994, Variable regions of Ig heavy chain genes encoding antithyrotropin receptor antibodies of patients with Graves’ disease, J. Immunol., 152, 1485, 10.4049/jimmunol.152.3.1485

Van Es J, 1992, A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene, J. Immunol., 149, 2234, 10.4049/jimmunol.149.6.2234

10.1006/clim.1999.4781

10.4049/jimmunol.1000445

10.1126/scitranslmed.3000540

10.3389/fimmu.2012.00193

10.1007/s10522-009-9256-9

10.1016/j.coi.2010.04.009

10.1016/j.coi.2014.05.003

10.1016/j.coi.2014.05.007

10.1016/j.coi.2014.03.007

10.1016/j.mad.2009.08.003

10.4049/jimmunol.175.5.3262

10.1038/ni.1814

10.1084/jem.20022020

10.1073/pnas.98.3.1166

10.1182/blood-2004-01-0346

Martin V, Age-related aspects of human IgM+ B cell heterogeneity, Ann. NY Acad. Sci

10.1182/blood-2014-04-571125

10.1093/nar/gkn316

Wilkins MR, 1999, Protein identification and analysis tools in the ExPASy server, Methods Mol. Biol., 112, 531

10.1111/j.1474-9726.2011.00732.x

10.1128/IAI.69.2.853-864.2001

10.1016/0167-5699(95)80009-3

10.1111/j.1365-2249.2007.03535.x

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Thông tin xuất bản

Philosophical Transactions of the Royal Society B: Biological Sciences

Tập 370 Số 1676

20140237

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