Naive non-obese diabetic (NOD/LtJ) mice spontaneously produce natural IgG autoantibodies against self-antigens associated with the experimental autoimmune diseases to which they are susceptible: insulin-dependant diabetes mellitus, systemic lupus erythematosus and experimental autoimmune encephalomyelitis. We discovered recently that NOD/LtJ mice also spontaneously produce IgG antibodies to the acetylcholine receptor (AchR), an antigen that can induce experimental autoimmune myasthenia gravis

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... AMG) in susceptible rodents. However, there are no reports indicating that NOD/LtJ mice are susceptible to EAMG. To test whether the presence of spontaneous IgG autoantibodies can predict susceptibility to an autoimmune disease, we challenged NOD/LtJ mice using a standard protocol to induce EAMG. We now report that NOD/LtJ mice developed EAMG, although to a somewhat lesser degree than did C57BL/6 mice, a strain regarded as highly susceptible to the disease. Both strains produced comparable levels of immune antibodies to AchR of the complement-®xing isotypes IgG2a and IgG2b; however, NOD/LtJ mice produced signi®cantly more IgG1. An antigen-speci®c T cell proliferative response to AchR of the same magnitude was detected in both strains, together with the secretion of similar amounts of IFN-g. Thus, NOD/LtJ mice are susceptible to EAMG and disease induction is accompanied by immune responses comparable to those seen in the susceptible strain C57BL/6. These results support the association between speci®c, natural IgG autoantibodies and susceptibility to the induction of a particular autoimmune disease. Methods Mice and antigens Eight-week-old female C57BL/6 and NOD/LtJ mice were bred in the animal facility of The Weizmann Institute of Science. The Correspondence to: I