PATHOGENESIS OF AUTOIMMUNITY IN MICE WITH SLE-LIKE ILLNESS

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Autoimmunity in New Zealand mice has a genetic and immune basis; however, severity of expression can be modified by viral and other environmental factors as well as sex hormones. The immune factors are complex. These include excessive B-cell activation and abnormal T cell function. A single gene, xid, prevents disease in congenic NZB and (NZB x NZW(F1 and BXSB mice, and markedly retards disease in MRL- 1pr/lpr mice. BXSB mice have a Y chromosome-linked gene which accelerate autoimmunity in autoimmune mice, but does not cause it in non-autoimmune mice. Studies of NZB, BXSB, MRL-lpr/lpr and normal mice show that the repertoires of their B cells are very similar suggesting that B cell activation in these mice is induced by polyclonal activation. Different autoimmune mice have increased expression of different cellular oncogenes. Lpr/lpr and gld/gld mice have increased myb and T cell receptor (Beta gene) mRNA. The xid gene prevents increased myc and ras expression characteristic of NZB and BXSB mice, suggesting that oncogene is associated with B cell activation and autoantibody production. The studies of gene expression in lpr/lpr mice have pointed to a new pathway for T cell maturation.