ANALYSIS OF VARIABLE REGION GENES ENCODING ANTI-SM AND ANTICARDIOLIPIN ANTIBODIES FROM A SYSTEMIC LUPUS-ERYTHEMATOSUS PATIENT

We have analysed the heavy and light chain variable region genes of tw o monoclonal antibodies, specific for the Sm antigen (RSP1; IgG kappa) and for cardiolipin (RSP4; IgM lambda), derived from a patient with a ctive systemic lupus erythematosus (SLE). We have established that the variable region genes of the RSP1 autoantibody are somatic mutants of two germ line genes from the V(H)4 and V kappa 1 gene families. RSP4 antibody uses gene segments closely related to a V(H)3 gene member and to a V lambda 1 gene. The presence and distribution of the somatic mu tations on both monoclonal autoantibodies are compatible with an antig en-driven immune process. These data suggest that in SLE a common anti genic stimulus may govern the autoantibody response against a wide spe ctrum of unrelated antigens, including native DNA, cardiolipin or Sm a ntigens, and provide further evidence that disease-associated autoanti bodies are generated through antigen-selected somatic mutations.