B cell depletion improves islet allograft survival with anti-CD45RB

A short course of anti-CD45RB leads to long-term islet allograft survival and donor-specific tolerance in approximately half of immunocompetent mice. We have previously demonstrated that anti-CD45RB antibody-mediated tolerance requires B cells for cardiac allograft survival. We therefore asked whether B cells were also required for anti-CD45RB antibody-mediated survival of islets. Unexpectedly, we found that nearly 100% of islet allografts survive long-term in B cell-deficient mice. Similarly, B cell depletion by anti-CD22/cal augmented anti-CD45RB mediated tolerance when administered pre-transplant, although it had no effect on tolerance induction when administered post-transplant. Our results demonstrate that the role of B cells in promoting tolerance with anti-CD45RB is graft-specific, promoting tolerance in cardiac grafts but resisting tolerance in islet transplantation. These findings may help elucidate the varied action of B cells in promoting tolerance versus rejection.