BENEFICIAL EFFECT OF POLYCLONAL IMMUNOGLOBULINS FROM MALARIA-INFECTEDBALB C MICE ON THE LUPUS-LIKE SYNDROME OF (NZB X NZW)F1 MICE/

We previously reported that infection of BALB/c mice with the parasite Plasmodium chabaudi induces high production of natural autoantibodies . Here we demonstrate that such an infection of lupus-prone (NZB x NZW )F1 (B/W) mice retards the development of their autoimmune disease. Su rvival and disease hallmarks (high-grade proteinuria and IgG anti-DNA antibodies) were delayed for 6 months when parasite inoculation was gi ven at either 3 or 7 months of age, i. e. before or after the onset of the clinical symptoms. Similar beneficial effects, although less pron ounced, were obtained when mice were treated with a total of 800 mu g of IgG (P-IgG) or IgM (P-IgM) or 300 mu g of cryoglobulin preparations isolated from P. chabaudi-infected BALB/c mice while similarly prepar ed fractions from uninfected mice had little effect. Compared to these fractions, P-IgG and P-IgM contained higher levels of natural antibod ies bearing the D23 idiotype characteristic of polyreactive natural au toantibodies with enhanced activity against Fab and Fc fragments of Ig G. In surviving mice, the level of anti-DNA antibodies, particularly t hose of IgG1 isotype, were significantly decreased. Flow cytometric an alysis of various T cell subsets showed that the number of cells expre ssing gamma delta T cell receptor (TcR) antigens which did not vary wi th age was not modified after P-IE;G or P-IgM treatment. In contrast, the number of T cells expressing V beta 8.1,2, V beta 10 and V beta 14 TcR antigens, which increased with age, were significantly reduced. T aken together, these results indicate that parasite infection of mice induces the synthesis of populations of IgM and IgG natural autoantibo dies with immunoregulatory properties and that these antibodies attemp t, at least transitorily, to rescue a natural autoantibody network tha t is deficient in B/W mice.