NOD B-cells are insufficient to incite T-cell-mediated anti-islet autoimmunity.

Although it is well established that B-cells are required for the development of diabetes in the nonobese diabetic (NOD) mouse, the nature of their role remains unknown. Herein, we investigate the hypothesis that B-cells in this autoimmune background actively disrupt the tolerant state of those T-cells with which they interact. We demonstrate that NOD B-cells express elevated levels of crucial molecules involved in antigen presentation (including CD21/35, major histocompatibility complex class II, and CD40), alterations that invite the possibility of inappropriate T-cell activation. However, when chimeric animals are generated in which all B-cells are NOD-derived, a tolerant state is maintained. These data demonstrate that although B-cells are required for the development of autoimmunity, they are not sufficient to disrupt established tolerance. Moreover, non-B-cell antigen-presenting cells may be the critical actors in the establishment of the tolerant state; this function may be absent in NOD mice as they are characterized by deficient professional antigen-presenting cell function.