Martin G. Weigert

My studies on the immune response to foreign antigens such as influenza have shown that antibody specificity is derived mainly from the combinatorial joining of gene segments, variation at the junctions of these segments, and after antigen selection and during clonal expansion-hypermutation. I have also examined the basis of autoantibody diversity in diseases such as lupus and rheumatoid arthritis and have found that the mechanisms that diversify and create specificity for self-antigens such as DNA are essentially the same as those that create specificity for foreign antigens. The implication of this result is that nonautoimmune individuals must actively regulate autoantibodies, a prediction I am testing using mice. I have discovered that healthy mice regulate autoreactive lymphocytes by secondary rearrangement of antibody genes, a process that I call "receptor editing." Currently, I am studying the efficiency of receptor editing in mouse models of Lupus.