Role of B Cells in Transplant Tolerance

Massachusetts General Hospital, Boston MA

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Abstract

DESCRIPTION (provided by applicant): The major impediments to the success of organ transplantation remain the failure of current immunosuppressive drugs to prevent rejection and the morbidities associated with the side effects of those drugs. Strategies for achieving tolerance would avoid both these problems. Most tolerance inducing protocols target the T cell compartment, especially regulatory T cells (Tregs) that can specifically suppress alloreactive immunity. However, recent studies suggest that there is an analogous subset of B cells in mice and humans. The combination of anti-CD45RB and anti-TIM1 results in almost 100% long term islet allograft survival, and this effect is dependent on the presence of recipient B cells. TIM1+ cells from tolerant mice are able to transfer tolerance to untreated animals in a donor specific manner. Tolerance transfer requires the presence of native Tregs in the second recipient. We hypothesize that combined antibody therapy induces a regulatory B cell population (Bregs) that interacts with Tregs to promote tolerance. This proposal seeks to elucidate the interaction of Bregs with Tregs and the molecules that are important in governing tolerance in this model.