Humoral autoimmunity in the pathogenesis of insulin-dependent diabetes mellitus. Studies in the spontaneously diabetic BB rat.

The present review describes the autoimmune aspects of the pathogenesis of insulin-dependent diabetes mellitus (IDDM) in man and in the BB rat, and the requirements for effective prevention. Using a xenotypic mouse islet cell antiserum, we demonstrated the presence of antibodies reacting specifically with the pancreatic beta cells and recognizing a Mr 40,000 plasma membrane glycoprotein. The existence of beta cell-specific surface antigens, which hypothetically could act as targets in an autoimmune response, might explain the selective disappearance of the beta cells in IDDM. The BB rat spontaneously develops an insulin-dependent diabetes much like IDDM in man. Diabetes in BB rats, as in IDDM of humans, is associated with a high incidence of islet cell surface antibodies. These antibodies precipitate a Mr 64,000 protein from lysates of islets of Langerhans isolated from normal rats. In the BB rat, islet cell antibodies precede the appearance of insulitis and the clinical onset of diabetes. We investigated the beneficial effects of early treatment with low doses of cortisone on diabetes in the BB rat, because comparable experiments in children with newly diagnosed IDDM have given inconclusive results. In the BB rat there was no effect on the incidence or severity of diabetes or on the diabetes-related, islet cell-directed autoimmune phenomena. However, immunologic intervention that prevents IDDM from developing in potentially susceptible individuals is a promising area for research on this disease.