The role of t/b lymphocyte collaboration in the regulation of autoimmune and alloimmune responses.

The present review highlights the two areas of research pursuit in our laboratory: (1). the regulation of the autoimmune T cell response to pancreatic islet beta cells using the nonobese diabetic (NOD) mouse model of type 1 diabetes and (2). the regulation the T cell response to alloantigens. Our work has established a central role for B lymphocytes in driving both autoimmune and allo-immmune T cell responses. Our studies indicate that: (1). B cell-deficient NOD mice are protected from autoimmune diabetes; (2). targeted disruption of cognate T/B cell collaboration via major histocompatibility complex (MHC) class II prevents both T cell-mediated islet destruction and allograft rejection; and (3). maternal transmission of islet-reactive autoantibodies potentiates the activation of diabetogenic T cells, highlighting the important role of B cells in the early targeting of islet beta cells.