REDUCTION IN DIABETES INCIDENCE IN AN I-A(G7) TRANSGENIC NONOBESE DIABETIC MOUSE LINE

Susceptibility to IDDM is strongly associated with major histocompatib ility complex (MHC) class II genotypes. Nonobese diabetic (NOD) mice d evelop a similar autoimmune diabetes and have a unique MHC class II I- A allele that is required for the development of diabetes. A number of groups have shown that the introduction of resistant MHC class II all eles as transgenes into the NOD mouse protects from diabetes. mie made control transgenic NOD mice, expressing their own I-A beta(g7) molecu le as a transgene. One of two lines of these mice showed a reduced inc idence of diabetes, without any change in T-cell proliferative respons e to a number of diabetes autoantigens or any change in insulitis seve rity. This line developed a subtle decrease in the percentage of splen ic B-cells that progressed with age. This defect was not associated wi th any other phenotypic abnormalities. Our findings suggest that asses sment of splenic B-cell number is necessary in interpretation of the e ffects of MHC class II transgenes on the development of diabetes in th e NOD mouse.