Spontaneously diabetic BB rats have age-dependent islet beta-cell-specific surface antibodies at clinical onset.
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 beta-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 complement-induced 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 beta-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 beta-cell-specific surface antibodies at onset of the disease. After 30 days of insulin treatment, beta-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 beta-cells compared with other islet cell types.(ABSTRACT TRUNCATED AT 250 WORDS)
Pipeleers
D
D
Department of Metabolism and Endocrinology, Vrije Universiteit Brussel, Belgium.
Van de Winkel
M
M
Dyrberg
T
T
Lernmark
A
A
D000375:Aging / Q000276:immunology*; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D007515:Islets of Langerhans / Q000276:immunology*; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains
D000954:Antigens, Surface; D001323:Autoantibodies; D003165:Complement System Proteins