IN THE ABSENCE OF A CD40 SIGNAL, B-CELLS ARE TOLEROGENIC

When B cells are deprived of signaling through CD40, they exhibit the ability to induce T cell tolerance. The in vivo administration of anti -gp39 and allogeneic B cells diminished the ability of mice to mount a n allogeneic response. Tolerance induction was specific for the haplot ype expressed on the allogeneic B cells. Selective allospecific unresp onsiveness was induced in the CD8 and CD4 compartments by the administ ration of anti-gp39 and class II-deficient B cells or class I-deficien t B cells, respectively. As predicted by studies with anti-gp39 treatm ent, diminished allospecific responsiveness was induced by the adminis tration of B cells to mice genetically deficient in gp39. Taken togeth er, these data are consistent with the premise that deprivation of CD4 0 signaling engenders B cells with enhanced tolerogenicity. These stud ies provide insights into the tolerogenic capacity of resting B cells and outlines a practical approach to exploit this function.