Neither B lymphocytes nor antibodies directed against self antigens of theislets of langerhans are required for development of virus-induced autoimmune diabetes

We evaluated the role of the humoral arm of the immune response in causing or contributing to virus-induced diabetes. Transgenic mire expressing the n ucleoprotein (NP) or glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCR IV) under control of the rat insulin promoter (RIP) in pancreati c beta cells (RIP-LCMV) and RIP-LCMV mice with genetic dysfunction of B cel ls (RIP-LCMV x mu MT/mu MT) were compared for development of diabetes after challenge with LCMV, After inoculation with LCMV, B and T lymphocytes and macrophages infiltrated into pancreatic islets in RIP-LCMV mice, and over 5 0% of these mice generated Abs against host insulin or glutamate decarboxyl ase. However, neither B cells nor the autoantibodies played a direct role i n the initiation, kinetics, or severity of the virus-induced diabetes as ju dged by comparing disease in RIP-LCR IV mice to littermates whose functiona l B cells were genetically eliminated. Furthermore, the quality and quantit y of T lymphocyte and macrophage infiltration was similar in the B cell-def icient and non-B cell-deficient RIP-LCMV mice. Although the development of autoantibodies to islet Ags had no direct influence on the pathogenesis of insulin-dependent (type 1) diabetes mellitus, it served as a prediabetes ma rker, as such autoantibodies were often elevated before the onset of diseas e. Hence, the RIP-LCMV model is not only useful for understanding the patho genetic mechanisms of how islets are destroyed and spared but also for eval uating therapeutic strategies before onset of clinical diabetes.