DIRECT EVIDENCE FOR THE CONTRIBUTION OF B-CELLS TO THE PROGRESSION OFINSULITIS AND THE DEVELOPMENT OF DIABETES IN NONOBESE DIABETIC MICE

The non-obese diabetic (NOD) mouse is an excellent animal model of aut oimmune diabetes associated with insulitis, The progression of insulit is causes the destruction of pancreatic beta cells, resulting in the d evelopment of hyperglycemia, Although it has been well documented that T cells are required for the development of insulitis and diabetes in NOD mice, the importance of B cells remains unclear, To clarify the r ole of B cells in the pathogenesis of NOD mice, we therefore generated B cell-deficient NOD (B-NOD) mice, Surprisingly, none (of 13) of the B-NOD mice developed diabetes by 40 weeks of age, while the control li ttermates with B cells (B+NOD) suffered from a high proportion (43 of 49) of diabetes, The insulin reactivity of B+NOD mice was significantl y impaired, while the B-NOD mice showed a good insulin response, thus suggesting the pancreatic beta cell function to be well preserved in B -NOD mice, Although B-NOD mice did develop insulitis, the extent of in sulitis was significantly suppressed, These data thus provide the dire ct evidence that B cells are essential for the progression of insuliti s and the development of diabetes in NOD mice.