Suppression of insulitis and diabetes in B cell-deficient mice treated with streptozocin: A cells are essential for the TCR clonotype spreading of islet-infiltrating T cells

In order to clarify the role of a cells in the development of insulitis and diabetes, a cell-deficient (B-) mice treated with streptozocin (STZ) were studied. The extent of insulitis and the cumulative incidence of diabetes w ere significantly suppressed in B- mice (P < 0.0001), indicating that a cel ls are crucial for the progression of insulitis and diabetes. Accumulation of both CD4(+) T cells and B cells was observed in islets of B+ mice, while CD4(+) T cells but not a cells were found in B- mice. A few CD8(+) T cells and macrophages were detectable in both types of mice. The immunohistochem ical study did not reveal any change in the subpopulations of infiltrating lymphocytes except for the absence of a cells in the B- mice. TCR V-beta ge ne repertoire usage of islet-infiltrating T cells was restricted to some ex tent in the B+ or B- mice, but there was no significant difference between the B+ and B- mice, suggesting that the initial islet-reactive T cell respo nse can occur in the absence of a cells. In contrast, TCR clonotype spreadi ng of islet-infiltrating T cells was significantly suppressed in B- mice co mpared with B+ mice (P< 0.0001), These data suggest that initial priming of T cells is not impaired arid TCR V-beta repertoire usage is not limited by the lack of a cells, while B cells are important essentially for the sprea ding of islet-infiltrating clonal T cells in autoimmune diabetic mice induc ed with STZ.