Antibodies spontaneously bound to islet cells in diabetic C57BL/KsJ db/db mice.

Antibodies to pancreatic islet cells were visualized, using an immunohistochemical method with the avidin-biotin-peroxidase complex, either in the islets or sera of diabetic C57BL/KsJ db/db mice. They were revealed within the cytoplasm of all islet cell types. Anti-islet complement-dependent antibodies were demonstrated in vitro in the sera of the same db/db mice. These anomalies were not detected in control littermates. During the life span of db/db mice, cell-bound antibodies were present at early stages, co-existing with hyperinsulinaemia, islet hypertrophy and decreased insulin content of cells. Circulating antibodies were detectable later, before the development of insulinopenia, islet atrophy and cell necrosis. The titre of the immunohistochemical detected complement-fixing antibodies and their lytic potency for islet cells in vitro increased with age. This is the first time that antibodies to islet cells have been revealed within the islets of diabetic animals. Furthermore, anti-islet cell autoantibodies appear very early in db/db islets and may be implicated in the pathogenesis of this murine diabetic syndrome.