Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice.

The non-obese diabetic (NOD) mouse is an excellent animal model of autoimmune diabetes associated with insulitis. The progression of insulitis causes the destruction of pancreatic b cells, resulting in the development 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 role of B cells in the pathogenesis of NOD mice, we therefore generated B celldeficient NOD (B ‐ NOD) mice. Surprisingly, none (of 13) of the B ‐ NOD mice developed diabetes by 40 weeks of age, while the control littermates with B cells (B F NOD) suffered from a high proportion (43 of 49) of diabetes. The insulin reactivity of B F NOD mice was significantly impaired, while the B ‐ NOD mice showed a good insulin response, thus suggesting the pancreatic b cell function to be well preserved in B ‐ NOD mice. Although B ‐ NOD mice did develop insulitis, the extent of insulitis was significantly suppressed. These data thus provide the direct evidence that B cells are essential for the progression of insulitis and the development of diabetes in NOD mice.