RHEUMATOID FACTORS FROM THE PERIPHERAL-BLOOD OF 2 PATIENTS WITH RHEUMATOID-ARTHRITIS ARE GENETICALLY HETEROGENEOUS AND SOMATICALLY MUTATED

We report the DNA sequences of the heavy and light chain immunoglobuli n genes of 11 monoclonal rheumatoid factor (RF)-secreting lines derive d from the peripheral blood of two patients with rheumatoid arthritis (RA). It is evident from immunogenetic analysis of these lines that RA -associated RF activity can arise from a wide variety of heavy and lig ht chain genes and gene combinations. Although the RF response from ou r two patients shows a bias in gene usage toward those genes used to e ncode monoclonal RF, particularly VkIII, relatively few of these RFs a re reactive with the monoclonal antiidiotypes 6B6.6 and 17.109 that de fine VkIII germline-encoded light chains and the loss of this idiotypi c reactivity is clearly related to somatic mutation. Finally, RFs deri ved from peripheral blood of RA patients show a similar heterogeneity of epitope binding to Fc as that seen for synovium-derived RF and some are clearly different in binding specificity from the restricted RF p opulation found in patients with B cell malignancies. Somatic mutation s as well as different VH/VL combinations contribute to the heterogene ity in the binding patterns of these RA-derived RF.