Rheumatoid factors (RFs) are
autoantibodies that are produced by approximately 75% of patients with
rheumatoid arthritis (RA). Their role in pathogenesis is not well understood. In this study of 81 human hybridoma
IgM antibodies derived from unstimulated peripheral blood B-cells of patients with RA and
systemic lupus erythematosus (SLE), we have demonstrated that idiotypes associated with RFs derived from patients with mixed
cryoglobulinemia were expressed by approximately 60% of RFs and 6% of
IgM antibodies lacking RF activity. The specificity of the RFs for the Fc portion of
IgG only (monospecificity) or for Fc and additional
self antigens (polyreactivity) was found to correlate with the expression of specific heavy chain associated idiotypes. The VH3 associated RF idiotypes, D12 and B6, were expressed by 0/16 (0%) of monospecific RFs compared with 6/22 (27%) of polyreactive RFs. The predominant use of VH3 was verified by analysis of the expressed Ig with VH family specific anti-
peptide antibodies. The light chains expressed by both populations of
IgM RFs were found to be predominantly VKIII, both by detection of specific
epitopes/idiotypes and V family analysis. This non-random gene usage of both the heavy and light chains suggests that there is a selective expression of V regions in the RF producing B-cells in patients with RA and SLE. We suggest that different
antigen-driven, clonal selection events may occur which result in either monospecific RFs or polyreactive RFs.