Islet graft survival in B-cell–deficient (µMT) and B-cell–depleted (anti-CD22/cal) mice in the three immune settings of islet transplantation (allo, auto, and allo/auto). 1) In allo, a delay in graft rejection was evident in B-cell–depleted mice compared with control-treated and untreated mice (P = 0.004) (A). 2) In auto, a prolongation of syngeneic graft survival was observed in B-cell–depleted mice compared with cal-treated (P = 0.006) and untreated mice (P = 0.03) (B). 3) In allo/auto, delayed graft rejection was achieved in B-cell–depleted mice compared with cal-treated (P = 0.003) and untreated mice (P = 0.001) (C). 4) When BALB/c islets were transplanted in chemically induced C57BL/6 B-cell–deficient mice, islet graft survival was significantly prolonged compared with WT C57BL/6 mice (P = 0.002) (D).