Diabetes induction by subdiabetogenic doses of streptozotocin in BALB/cBOM mice. Noninvolvement of host B-lymphocyte functions.

Abstract

Multiple subdiabetogenic doses of streptozotocin induce an insulin-dependent progressive hyperglycemia in genetically susceptible strains of mice. We have shown previously that T-cell-dependent autoimmune mechanisms play an obligatory role in this model of diabetogenesis by demonstrating that athymic nude mice and lethally irradiated euthymic mice are selectively resistant to diabetes induction and that the susceptibility can be reconstituted by grafting thymus in nude mice or by giving B-cell-depleted splenic lymphocytes to the irradiated mice. In this report we investigate more directly the possible role of host B-cell functions in the induction of hyperglycemia. Mice were rendered selectively deficient in functional B lymphocytes by repeated injections of a polyclonal antiserum against mouse IgM, starting immediately after birth. These B-cell-suppressed mice had no detectable ability to produce antibodies against a test antigen but appeared to have normal levels of T cells. When treated with multiple low doses of streptozotocin, they developed progressive hyperglycemia in a manner indistinguishable from control mice with normal B-cell functions. These results suggest that host B cells, in contrast to host T cells, are not etiologically involved in the development of diabetes induced by multiple subdiabetogenic doses of streptozotocin.