Xie, X orcid.org/0000-0002-1474-9931, Shrimpton, J, Doody, GM orcid.org/0000-0003-0665-6759 et al. (2 more authors) (2021) B-cell capacity for differentiation changes with age. Aging Cell, 20 (4). e13341. ISSN 1474-9718
Abstract
Background
Age-related immune deficiencies are thought to be responsible for increased susceptibility to infection in older adults, with alterations in lymphocyte populations becoming more prevalent over time. The loss of humoral immunity in ageing was attributed to the diminished numbers of B cells and the reduced ability to generate immunoglobulin.
Aims
To compare the intrinsic B-cell capacity for differentiation into mature plasma cells (PCs), between young and old donors, using in vitro assays, providing either effective T-cell help or activation via TLR engagement.
Methods
B cells were isolated from healthy individuals, in younger (30–38 years) and older (60–64 years) donors. An in vitro model system of B-cell differentiation was used, analysing 5 differentiation markers by flow cytometry, under T-dependent (TD: CD40/BCR stimulation) or T-independent (TI: TLR7/BCR activation) conditions. Antibody secretion was measured by ELISA and gene expression using qPCR.
Results
TI and TD differentiation resulted in effective proliferation of B cells followed by their differentiation into PC. B-cell-executed TI differentiation was faster, all differentiation marker and genes being expressed earlier than under TD differentiation (day 6), although generating less viable cells and lower antibody levels (day 13). Age-related differences in B-cell capacity for differentiation were minimal in TD differentiation. In contrast, in TI differentiation age significantly affected proliferation, viability, differentiation, antibody secretion and gene expression, older donors being more efficient.
Conclusion
Altogether, B-cell differentiation into PC appeared similar between age groups when provided with T-cell help, in contrast to TI differentiation, where multiple age-related changes suggest better capacities in older donors. These new findings may help explain the emergence of autoantibodies in ageing.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | ageing; B-cell differentiation; T-cell dependent; T-cell independent |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Musculoskeletal Medicine & Imaging (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Feb 2021 14:43 |
Last Modified: | 25 Jun 2023 22:35 |
Status: | Published |
Publisher: | Wiley Open Access |
Identification Number: | 10.1111/acel.13341 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:171468 |