EFFECT OF MHC TRANSGENE EXPRESSION ON SPONTANEOUS INSULIN AUTOANTIBODY CLASS SWITCH IN NONOBESE DIABETIC MICE

A study of spontaneous anti-insulin autoantibodies in nonobese diabeti c (NOD) mice revealed that when first detected, the antibodies are imm unoglobulin M (IgM), but by age 10 weeks, immunoglobulin G (IgG) autoa ntibodies have appeared in many of these animals, When NOD strains, pa rtially or completely protected from IDDM by the insertion of transgen es in the class II region, were compared, it was found that the switch to IgG autoantibodies was inhibited and the autoantibodies remained I gM indefinitely, We speculate that the switch to IgG may be a marker o f events leading to IDDM in NOD mice and an indication that T-cell hel p has been generated for responses to beta-cell antigens, Such help no t only directs the development of IgG autoantibodies, but more importa ntly, allows the emergence of potentially pathogenic T-cell clones tha t are capable of infiltrating the pancreas and mediating beta-cell dam age.