SYNOVIAL IGG RHEUMATOID FACTORS SHOW EVIDENCE OF AN ANTIGEN-DRIVEN IMMUNE-RESPONSE AND A SHIFT IN THE V-GENE REPERTOIRE COMPARED TO IGM RHEUMATOID FACTORS

We have established IgG rheumatoid factor (RF)-secreting hybridoma cel l lines from the synovial tissues of three patients from whom we have previously characterized several IgM RF. The IgG PF bind human and rab bit IgG and form intracellular complement-fixing complexes indicative of a self association process in vivo. Nucleotide sequence analysis re vealed that two IgG RF used V(H)III gene segments, while one used a V( H)I gene segment. The V(L) gene usage consisted of a Vkappa1, a Vlambd a2 and a Vkappa4/Vkappa6 hybrid, confirming our previous findings that many different V(L) genes can contribute to RF specificity. Although the IgG RF used V(H) genes from the same families that dominated the I gM RF response, two of the actual gene segments employed were not foun d among the IgM RF. In contrast to IgM RF, which in general were not v ery mutated, the IgG RF showed somatic mutations characteristic of an antigen-driven immune response.