Preferential utilization of a novel vλ3 gene in monoclonal rheumatoid factors derived from the synovial cells of rheumatoid arthritis patients

Objective. To further our understanding about the molecular genetics of rheumatoid factor (RF) in rheumatoid arthritis (RA). Methods. The heavy and light chain variable region (V) genes of 5 new human monoclonal IgM RFs were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide termination method. Results. The results reveal the recurrent usage in two RA patients of a novel Vλ3 germline gene, designated Humlv3c93. Specifically, in 2 of 3 RFs (C93 and D53) from one patient, the light chains in the Vλ gene-encoded region were identical to each other and to the light chain of an RF (H4) from another patient. Serologically, the light chains of these 3 RFs were classified as members of the Vλ3b sub-subgroup. Each of the RFs was encoded by a different VH gene. Both C93 and D53 bound specifically with human and rabbit IgG, whereas H4 was monospecific for rabbit IgG. Conclusion. Since the 1v3c93 gene is not homologous to any reported Vλ sequence from natural auto-antibodies, it is possible that 1v3c93 may represent a disease-specific RF-related Vλ gene. Moreover, the amino acid sequence CSGGSCY in the third complementarity-determining regions of 2 of the RF heavy chains is encoded by the DLR2 gene segment and has been found previously in 2 other RA-derived RFs, and thus may play a significant role in antigen binding.