B cells as antigen-presenting cells in transplantation rejection and tolerance

Abstract

Transplantation of fully allogeneic organs into immunocompetent recipients invariably elicits T cell and B cell responses that lead to the production of donor-specific antibodies (DSA). When immunosuppression is inadequate donor-specific T cell and B cell responses escape, leading to T cell-mediated rejection (TCMR), antibody mediated (ABMR) rejection, or mixed rejection (MR) exhibiting features of both TCMR and ABMR. Current literature suggests that ABMR is a major cause of late graft loss, and that new therapies to curtail the donor-specific humoral response are necessary. The majority of research into B cell responses elicited by allogeneic allografts in both preclinical models and clinical studies, has focused on the function of B cells as antibody-secreting cells and the pathogenic effects of DSA as mediators of ABMR. However, it has long been recognized that the DSA response to allografts is T cell-dependent, and that B cells engage in cognate interactions with T cells that provide "help" and promote B cell differentiation into antibody-secreting cells (ASCs). This review focusses the function of B cells as antigen-presenting cells (APCs) to T cells in lymphoid organs, how they may be critical APCs to T cell in the allograft, and the functional consequences of these interactions.