PREFERENTIAL UTILIZATION OF A NOVEL V-LAMBDA-3 GENE IN MONOCLONAL RHEUMATOID FACTORS DERIVED FROM THE SYNOVIAL-CELLS OF RHEUMATOID-ARTHRITIS PATIENTS

Objective. To further our understanding about the molecular genetics o f rheumatoid factor (RF) in rheumatoid arthritis (RA). Methods. The he avy and light chain variable region (V) genes of 5 new human monoclona l IgM RFs were cloned and sequenced using the polymerase chain reactio n and the dideoxynucleotide termination method. Results. The results r eveal the recurrent usage in two RA patients of a novel V lambda 3 ger mline gene, designated Humlv3c93. Specifically, in 2 of 3 RFs (C93 and D53) from one patient, the light chains in the V lambda gene-encoded region were identical to each other and to the light chain of an RF (H 4) from another patient. Serologically, the light chains of these 3 RF s were classified as members of the V lambda 3b sub-subgroup. Each of the RFs was encoded by a different VH gene. Both C93 and D53 bound spe cifically with human and rabbit IgG, whereas H4 was monospecific for r abbit IgG. Conclusion. Since the lv3c93 gene is not homologous to any reported V lambda sequence from natural autoantibodies, it is possible that lv3c93 may represent a disease-specific RE-related V lambda gene . Moreover, the amino acid sequence CSGGSCY in the third complementari ty-determining regions of 2 of the RF heavy chains is encoded by the D LR2 gene segment and has been found