Cross-reactive antibodies have both protective and pathogenic potential.

We report the characteristics of five IgM anti-phosphorylcholine (PC) Abs derived from nonautoimmune BALB/c mice. These Abs were chosen on the basis of their unique ability to cross-react with dsDNA. Three Abs protect mice from a lethal pneumococcal infection, and all five Abs deposit in glomeruli and cause renal dysfunction. Analysis of V region gene usage shows that none of the Abs is encoded by the V1 gene segment used to encode the dominant T15+ anti-PC response typically expressed in serum of PC-immunized BALB/c mice. The demonstration of the existence of noncanonical protective anti-PC Abs that also display pathogenic autoreactivity suggests that idiotypically restricted responses may serve to prevent the expression of Abs that react with both foreign and self Ags and so help maintain self-tolerance.