A cytotoxic monoclonal islet cell surface antibody from the NOD mouse.
Monoclonal antibody (Mab) 1.93B7 was obtained by fusion of spleen cells from a diabetic NOD mouse with P3X63Ag8.653 myeloma cells and screening for complement mediated lysis of rat insulinoma (RIN) cells. Immunofluorescence studies revealed that this Mab binds to RIN cells but not to the rat pituitary tumour line GH3. The binding of Mab 1.93B7 to RIN cells was abolished by trypsin but not by neuraminidase treatment of the cells, suggesting that the antigen recognized is a protein. Mab 1.93B7 bound to approximately 30% of mouse (BALB/c) and rat islet cells which had been subjected to trypsin digestion and incubated as a single cell suspension for 12h to allow reexpression of trypsin sensitive antigens. Since Mab 1.93B7 is potentially pathogenic, as suggested by its reactivity to primary islet cells and its complement fixing capacity, we injected it into BALB/c and NOD mice. Cytotoxic activity against RIN cells was detected in the serum of the animals injected with Mab 1.93B7, but the Mab did not exert a diabetogenic action and failed to reverse diabetes when administered at onset in NOD mice. No modification of the course of spleen cell mediated transfer of diabetes in NOD mice was observed when the Mab was administered from the time of spleen cell inoculation to the appearance of glycosuria. The implications of the lack of an effect in vivo of Mab 1.93B7 under the conditions employed are discussed.
Pontesilli
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Barbara Davis Center for Childhood Diabetes, Department of Microbiology and Immunology, University of Colorado Health Sciences Center, Denver 80262.
Carotenuto
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Hayward
A R
AR
Prowse
S J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D005260:Female; D007116:Immunization, Passive; D007340:Insulinoma / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; C024211:islet cell antibody