EVIDENCE FOR ANTIGEN-DRIVEN SELECTION IN 2 MONOCLONAL AUTOANTIBODIES DERIVED FROM NONOBESE DIABETIC MICE

The nonobese diabetic (NOD) mouse is a model of human type I diabetes. This diabetes is due to massive infiltration of the pancreatic beta c ell of islets by autoreactive T cells (insulitis) followed by the dest ruction of insulin-producing cells. Circulating autoantibodies are als o detected, notably against glutamic acid decarboxylase, peripherin an d insulin. Two monoclonal autoantibodies directed against insulin and peripherin were obtained by fusing NOD spleen and myeloma cells. We re port here the nucleotide sequence of the genes encoding for the V regi ons of these two antibodies. Somatic mutations were identified by comp aring the light chain nucleotide sequence of one of these autoantibodi es with its germline counterpart precursor established from NOD mice a fter PCR gene amplification. The other one displays N additions on bot h sides of the D region. These results strongly suggest that both auto antibodies have undergone diversification, either N additions or somat ic mutations, and therefore present structural features of antibodies derived from animals immunized against exogenous antigens.