B lymphocytes contribute to indirect pathway T cell sensitization via acquisition of extracellular vesicles. Issue 4 (10th July 2020)

• Record Type: Journal Article
• Authors: Becker, Pablo D.; Ratnasothy, Kulachelvy; Sen, Monica; Peng, Qi; Romano, Marco; Bazoer, Jordan; Suvitra, Erik; Stout, Anas; Hylton, Shannon G.; Dorling, Anthony; Lechler, Robert I.; Smyth, Lesley A.; Lombardi, Giovanna
• Is Part Of: American journal of transplantation. Volume 21:Issue 4(2021)
• Page Start: 1415
• Page End: 1426
• Publication Date: 2020-07-10
• Subjects: animal models: murine -- antigen presentation/recognition -- B cell biology -- immune regulation -- immunobiology -- immunosuppression/immune modulation -- translational research/science; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16088
• Languages: English
• ISSNs: 1600-6135

Abstract

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 (K d ) 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 K d skin transplant. T cell proliferation was markedly inhibited in the absence of recipient B cells, suggesting that B cells contribute to indirect pathway sensitization. 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 regulatory T cells (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 emphasizes the advantage of combination therapies in prolonging transplant survival. Abstract : Depletion of B cells prior to transplantation prolongs skin graft survival, reflecting their role in sensitizing indirect pathway T cells after acquisition of MHC alloantigens delivered by extracellular vesicles. See page 1361 for an editorial from Colas and Brouard.