Experimental models of B cell tolerance in transplantation - PubMed (original) (raw)

Review

Experimental models of B cell tolerance in transplantation

Michelle L Cowan et al. Semin Immunol. 2012 Apr.

Abstract

The use of conventional immunosuppression has successfully improved short-term allograft survival, however, long-term allograft survival has remained static and is complicated by serious side effects secondary to the long-term use of immunosuppressive agents. Immunological tolerance is the ultimate goal of organ transplantation, however it is an infrequent event in humans. Accordingly, over the past several decades, there has been a push to fully understand both the cellular and molecular mechanisms that play a role in the induction and maintenance of tolerance, with recent data implicating B cells and donor specific alloantibody as a barrier to and potential mediator of allograft tolerance. The study of B cells and alloantibody in transplant tolerance has evolved over recent years from using rodent models to non-human primate models. This review will discuss the role of B cells and alloantibody as antagonists and facilitators of transplantation tolerance, and highlight the experimental models developed for elucidating the mechanisms of B cell tolerance to alloantigen.

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Figures

Figure 1

Antibodies play diverse roles in allograft rejection. Following allograft transplantation, alloreactive B cells are activated and differentiate into antibody secreting plasma cells. The secreted antibodies bind to alloantigen expressed on the graft endothelial cells to mediate humoral rejection via complement-dependent and antibody-dependent cellular cytotoxicity (ADCC) mechanisms, the latter involving FcγR-bearing natural killer cells. Alternatively, donor cells or cell fragments can be bound by antibodies to form opsonins, which are then engulfed by recipient FcγR-bearing macrophages and dendritic cells. Within these antigen presenting cells (APC), donor antigen is processed and presented in the context of MHC class I and II to recipient CD8+ or CD4+ T cells, respectively. These indirectly primed alloreactive effector T cells then mediate cellular rejection of the allograft. Both humoral and cellular processes can occur concurrently to induce mixed antibody and cell-mediated rejection.

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Experimental models of B cell tolerance in transplantation - PubMed (original) (raw)