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. https://doi.org/10.1111/ajt.16088
AuthorsBecker, 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.
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.

JournalAmerican Journal of Transplantation
ISSN1600-6135
Year2020
PublisherWiley for American Society of Transplantation and the American Society of Transplant Surgeons
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Digital Object Identifier (DOI)https://doi.org/10.1111/ajt.16088
Web address (URL)https://doi.org/10.1111/ajt.16088
Publication dates
Online06 Jun 2020
Publication process dates
Accepted21 May 2020
Deposited11 Jun 2020
FunderBritish Heart Foundation
Rosetrees Trust
University of East London
National Institue for Health Research
Copyright holder© 2020 The Authors.
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