A comparative immunologic analysis of several murine strains with autoimmune manifestations

Abstract

The genetic autoimmune disease (lupus-like) in mice of several strains (NZB, NZB × W, MRL 1 , MRL n , BXSB) has been analyzed comprehensively. Comparison of the histoimmunopathologic, serologic, and cellular characteristics of these mice reveals several pathogenic common denominators but no obvious etiologic factors in common. In all kinds of autoimmune mice studied, the lupus-like syndrome consists of a fatal immune complex glomerulonephritis, thymic atrophy, and lymphoid hyperplasia that varies in degree. The lymphoid hyperplasia is most prominent in MRL 1 mice and it is of T-cell origin. MRL 1 mice, in addition, may exhibit arteritis and arthritis. Serologically, all SLE mice have abnormally elevated serum Ig levels, antinuclear antibodies, anti-ds- and ssDNA antibodies, and anti-hapten antibodies. Some of the MRL 1 mice, in addition to the above antibodies, develop antibodies to Sm ( MRL 1 and MRL n ) and antiglobulins ( MRL 1 ). Natural thymocytotoxic antibodies and anti-erythrocyte antibodies are predominantly found in NZB and NZB × W mice. With advanced age and disease all lupus mice have depressed complement levels and circulating immune complexes. Some of these complexes in all lupus mice are composed of retroviral gp70-anti-gp70 antibodies, whereas MRL 1 mice, in addition, contain circulating IgG-IgG RF complexes. Characterizing the various recognized lymphoid cell surface markers, one notes that each strain of lupus mice has some variation from the normal distribution, but in no two of these strains are the abnormalities the same. The B cells of these mice seem advanced in maturity, whereas the developmental isotype diversity is normal in all of them. NZB and NZB × W mice are characterized by a nonspecific early B-cell hyperactivity but it is not known if this activity is responsible for their subsequent specific autoantibody production. The proliferating T cells of older MRL 1 mice seem to exert excessive helper activity on syngeneic B cells. Both antigen-specific and antigen-nonspecific Con A-induced suppression are within normal limits in all lupus mice. Although transfer studies have shown that the basic defect is associated with the lymphoid system, from our work and that of others it appears that the abnormalities in these mice are polygenic and different from one strain to another. Thus, murine lupus as a syndrome can be the result of many different abnormalities which eventuate in B-cell hyperactivity and involvement of a number of the available endogenous antigens in a systemic immune complex disease which is responsible for the “characteristic” clinical picture of systemic lupus erythematosus.