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 cell lines from the synovial tissues of three patients from whom we have previously characterized several IgM RF. The IgG PF bind human and rabbit IgG and form intracellular complement-fixing complexes indicative of a self association process in vivo. Nucleotide sequence analysis revealed 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 Vlambda2 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 IgM RF response, two of the actual gene segments employed were not found among the IgM RF. In contrast to IgM RF, which in general were not very mutated, the IgG RF showed somatic mutations characteristic of an antigen-driven immune response.