B lymphocytes contribute to indirect pathway T cell sensitisation via acquisition of extracellular vesicles
Article
Becker, P. D., Ratnasothy, K., Sen, M., Peng, Q., Romano, M., Bazoer, J., Suvitra, E., Stout, A., Hylton, S. G., Dorling, A., Lechler, R. I., Smyth, L. and Lombardi, G. 2020. B lymphocytes contribute to indirect pathway T cell sensitisation via acquisition of extracellular vesicles. American Journal of Transplantation. 21 (4), pp. 1415-1426. https://doi.org/10.1111/ajt.16088
Authors | Becker, P. D., Ratnasothy, K., Sen, M., Peng, Q., Romano, M., Bazoer, J., Suvitra, E., Stout, A., Hylton, S. G., Dorling, A., Lechler, R. I., Smyth, L. and Lombardi, G. |
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Abstract | B cells have been implicated in transplant rejection via antibody‐mediated mechanisms and more recently by presenting donor‐antigens to T cells. We have shown in patients with chronic antibody‐mediated rejection that B cells control the indirect T cell alloresponses. To understand more about the role of B cells as antigen presenting cells for CD4⁺ T cell with indirect allospecificity, B cells were depleted in C57BL/6 mice, using an anti‐CD20 antibody, prior to receiving MHC‐class I‐mismatched (Kᵈ) skin. The absence of B cells at the time of transplantation prolonged skin graft survival. To study the mechanisms behind this observation, T cells with indirect allospecificity were transferred in mice receiving a Kᵈ skin transplant. T cell proliferation was markedly inhibited in the absence of recipient B cells, suggesting that B cells contribute to indirect pathway sensitisation. Furthermore, we have shown that a possible way in which B cells present alloantigens is via acquisition of MHC‐peptide complexes. Finally, we demonstrate that the addition of B cell depletion to the transfer of Tregs with indirect alloresponse further prolonged skin graft survival. This study supports an important role for B cells in indirect T cell priming and further emphasises the advantage of combination therapies in prolonging transplant survival. |
Journal | American Journal of Transplantation |
Journal citation | 21 (4), pp. 1415-1426 |
ISSN | 1600-6135 |
Year | 2020 |
Publisher | Wiley for American Society of Transplantation and the American Society of Transplant Surgeons |
Accepted author manuscript | License File Access Level Repository staff only |
Publisher's version | License File Access Level Anyone |
Supplemental file | File Access Level Anyone |
Supplemental file | File Access Level Anyone |
Digital Object Identifier (DOI) | https://doi.org/10.1111/ajt.16088 |
Publication dates | |
Online | 06 Jun 2020 |
Publication process dates | |
Accepted | 21 May 2020 |
Deposited | 11 Jun 2020 |
Funder | British Heart Foundation |
Rosetrees Trust | |
University of East London | |
National Institue for Health Research | |
Copyright holder | © 2020 The Authors. |
https://repository.uel.ac.uk/item/881v9
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