In order to clarify the role of B cells in the development of insulitis and diabetes, B cell-deficient (B-) mice treated with streptozocin (STZ) were studied. The extent of insulitis and the cumulative incidence of diabetes were significantly suppressed in B- mice (P<0.0001), indicating that B cells 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 B cells were found in B- mice. A few CD8+ T cells and macrophages were detectable in both types of mice. The immunohistochemical study did not reveal any change in the subpopulations of infiltrating lymphocytes except for the absence of B cells in the B- mice. TCR Vβ gene repertoire usage of islet-infiltrating T cells was restricted to some extent 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 response can occur in the absence of B cells. In contrast, TCR clonotype spreading of islet-infiltrating T cells was significantly suppressed in B- mice compared with B+ mice (P<0.0001). These data suggest that initial priming of T cells is not impaired and TCR Vβ repertoire usage is not limited by the lack of B cells, while B cells are important essentially for the spreading of islet-infiltrating clonal T cells in autoimmune diabetic mice induced with STZ.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy