Immunization of mice with purified U1 small nuclear ribonucleoprotein (RNP) induces a pattern of antibody specificities characteristic of the anti-Sm and anti-RNP autoimmune response of patients with lupus erythematosus, as measured by monoclonal antibodies.

Sera of patients with systemic lupus erythematosus and related autoimmune diseases often possess anti-Sm and anti-ribonucleoprotein (RNP) autoantibodies that recognize antigenic sites on small nuclear (sn) RNPs containing the snRNAs U1, U2, U4, U5, and U6. Although the major immunoreactive Sm polypeptides B', B, and D are present in snRNPs U1-U6, the RNP-antigenic proteins termed 70 kDa, A, and C are found only in U1 snRNP particles. We have immunized genetically nonautoimmune C57BL/6 mice with isolated human U1 snRNP particles and found that the major RNP and Sm antigenic polypeptides are also primarily immunogenic in the experimental immune response. Monoclonal antibodies (mAbs) derived from the mice thus immunized reacted specifically with polypeptides 70 kDa or A or recognized the Sm polypeptides B', B, and D simultaneously. One mAb reacted with an epitope shared by the U1 RNP polypeptide A and the U2 RNP polypeptide B". Competitive binding studies with the mAbs and anti-RNP/Sm patient sera indicated that the mAbs recognize the same regions on the antigenic snRNP polypeptides as the autoantibodies. This shows that B cells capable of producing autoantibodies against snRNPs are in principle present in the normal immune system. The striking similarity that we observed between the antibody pattern produced by the mice against exogenous U1 snRNP particles and that of systemic lupus erythematosus patients suggests the possibility that the anti-Sm and anti-RNP autoimmune response may be triggered by the endogenous U snRNPs rather than by a crossreacting viral or bacterial neoantigen. The possibility of eliciting anti-RNP and -Sm-type autoantibodies against exogenous snRNPs in normal mice should also allow potential pathogenic effects of such circulating antibodies to be investigated.