Diabetes-prone BB rats were examined before, during, and after clinical onset of diabetes for the occurrence of circulating islet cell surface antibodies (ICSAs) with a specific binding to islet β-cells. The presence of ICSA was assessed by incubating serum immunoglobulin fractions with normal Wistar rat islet cells and identifying cell-bound immunoglobulins by indirect immunofluorescence and by a complementinduced cell toxicity reaction. Under the selected experimental conditions, none of the diabetes-resistant rats were ICSA positive over the entire study period (45–120 days of age). In two diabetes-prone BB rat strains, 19 animals developed diabetes with onset between 50 and 120 days. At day 45, none of these animals was positive for ICSA. In rats developing diabetes between 50 and 85 days of age, 7 of 9 animals presented ICSA at clinical onset, determined by either the immunofluorescence or cytotoxicity test. The antibodies bound to insulin-containing β-cells but not to other islet cell types, and binding was not eliminated by absorption with liver powder. In animals developing diabetes between 85 and 120 days, only 1 of 10 was positive for β-cell-specific surface antibodies at onset of the disease. After 30 days of insulin treatment, β-cell-specific antibodies were detectable in 3 of 4 animals of age 50-85 days, whereas only 3 of 12 older rats presented ICSAs that were, in addition, of low titer or affinity. Our data confirm that ICSAs develop in diabetic BB rats and indicate that these antibodies can bind specifically to islet 7bgr;-cells compared with other islet cell types. Our study also suggests that the occurrence of circulating β-cell-specific surface antibodies in diabetes-prone BB rats is not only related to the time of clinical onset of the disease but also to the age of the animals. Our study illustrates the advantage of using purified normal islet cells in the analysis of the autoimmune phenomena in insulin-dependent diabetes.

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