Anti-CD45RB/Anti-TIM-1-Induced Tolerance Requires Regulatory B Cells

The role of B cells in transplant tolerance remains unclear. Although B-cell depletion often prolongs graft survival, sometimes it results in more rapid rejection, suggesting that B cells may have regulatory activity. We previously demonstrated that tolerance induction by anti-CD45RB antibody requires recipient B cells. Here, we show that anti-CD45RB in combination with anti-TIM-1 antibody has a synergistic effect, inducing tolerance in all recipients in a mouse islet allograft model. This effect depends on the presence of recipient B cells, requires B-cell IL-10 activity, and is antigen-specific. These data suggest the existence of a regulatory B-cell population that promotes tolerance via an IL-10-dependent pathway.