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 × NZW)F1 (B/W) mice retards the development of their autoimmune disease. Survival and disease hallmarks (high‐grade proteinuria and IgG anti‐DNA antibodies) were delayed for 6 months when parasite inoculation was given at either 3 or 7 months of age, i.e. before or after the onset of the clinical symptoms. Similar beneficial effects, although less pronounced, were obtained when mice were treated with a total of 800 m̈g of IgG (P‐IgG) or IgM (P‐IgM) or 300 m̈g of cryoglobulin preparations isolated from P. chabaudi‐infected BALB/c mice while similarly prepared fractions from uninfected mice had little effect. Compared to these fractions, P‐IgG and P‐IgM contained higher levels of natural antibodies bearing the D23 idiotype characteristic of polyreactive natural autoantibodies with enhanced activity against Fab and Fc fragments of IgG.

In surviving mice, the level of anti‐DNA antibodies, particularly those of IgG1 isotype, were significantly decreased. Flow cytometric analysis of various T cell subsets showed that the number of cells expressing γδ T cell receptor (TcR) antigens which did not vary with age was not modified after P‐IgG or P‐IgM treatment. In contrast, the number of T cells expressing Vβ8.1,2, Vβ10 and Vβ14 TcR antigens, which increased with age, were significantly reduced. Taken together, these results indicate that parasite infection of mice induces the synthesis of populations of IgM and IgG natural autoantibodies with immunoregulatory properties and that these antibodies attempt, at least transitorily, to rescue a natural autoantibody network that is deficient in B/W mice.