[An experimental study of spontaneously diabetic Bio Breeding/Worcester (BB/W) rats--with special references to the rat MHC (RT1) in the development of the disease].

The role of rat MHC (RT1) in the development of diabetes mellitus was studied on the Bio Breeding/Worcester (BB/W) rat, an experimental model animal for human juvenile onset (Insulin-dependent, Type 1) diabetes mellitus. The rate of the development of diabetes mellitus was as follows; 35/45 (77.8%) in inbred BB/W rats (u/u haplotype), and 5/397 (1.7%) in F2 rats. Histopathological examinations demonstrated that there were lymphocytic thyroiditis, T cell depletion in the spleen and in the lymph nodes, and extramedullary hematopoiesis, in addition to typical lymphocytic insulitis in the pancreas. Immunohistochemically, the expression of class II antigens in the pancreas was shown to be highly concerned with the histopathological changes and the clinical onset of the diabetes mellitus. Analysis of subsets of infiltrating cells demonstrated that macrophages appeared in the pancreas prior to the onset of the disease. And it was suggested that the infiltrated OX 6+ macrophages functioned as antigen presenting cells, leading to expression of the class II antigens on the surface of islet cells, and finally caused severe lymphocytic insulitis. However, BB/W rats showed complete negative immunohistochemical stainings with a monoclonal antibody HOK 2B, which stained other rat strains carrying RT1u class II antigen (TO, SDJ). Moreover, differences in blocking effect of HOK 2B were found on mixed lymphocyte reactions (MLR) between BB/W and other strains with RT1u haplotype. These findings raise the possibility that minor heterogeneities exist in the structure of class II molecules in RT1u rats including BB/W, which might be closely related to the onset of the disease.