No abstract

Objective. Understanding the molecular genetic basis for rheumatoid factor (RF) production is necessary to a better understanding of the etiology and pathogenesis of rheumatoid arthritis (RA). We sought to define the genetic basis of RF in RA.Methods. The heavy and light chain variable region genes encoding 4 human monoclonal RF were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide chain-termination method. Submitted for publication April 7, 1992; accepted in revised form July 7, 1992. D5 and 6 4 strongly suggest that these 2 RFs arise in an antigen-driven response in rheumatoid synovium. The presumed germline V genes for C6 may represent diseasespecific RF-related V genes.

Rheumatoid factors (RFs) are anti-IgG autoantibodies, and are found in patients with rheumatoid arthritis and normal individuals (reviewed in reference 1) . Previously (2, 3), we prepared two antiidiotypic antibodies by immunization with two synthetic peptides (PSL2 and PSL3), corresponding to the second and the third complementarity determining regions (CDRs) of the Wa crossreact idiotype (CRI)-positive RF Sie light chain. When a total of 24-25 human monoclonal IgM RFs were analyzed, anti-PSL2 and anti-PSL3 reacted with 20 and 15 RFs, respectively. Furthermore, amino acid sequence analysis of 9 PSL2 and PSL3 CRI+ RF light chains revealed that they share 89-96 of96 amino acid residues (4). These results suggested that the CRI* positive RF light chains were encoded by a single conserved V, gene. This contention was supported by the recent isolation from normal human placenta of a VK gene (designated