RESTRICTED DIVERSITY OF THE VARIABLE REGION NUCLEOTIDE-SEQUENCES OF THE HEAVY AND LIGHT-CHAINS OF A HUMAN RHEUMATOID-FACTOR

The complete nucleotide sequences of the variable region genes of the heavy and light polypeptide chains of a human monoclonal rheumatoid factor (RF) produced from a human-mouse heterohybridoma were determined. The antibody, designated YES8c, contained V(k)III, J(k)2, V(H)1, J(H)4, and a D gene segment of 9 amino acids. The nucleotide sequences and the deduced amino acid sequences of the light chain variable region were remarkably homologous (97-98%) to previously described RF of the Wa idiotypic family (PAY, GLO, CUR, FLO, and GAR) and to that of a V(k)III germline gene (Humkv325). The YES8c heavy chain variable region gene was most closely related to the V(H)1 gene of the restricted human fetal repertoire, designated 51p1, and also to 3 rearranged V(H)1 genes that were recently isolated from patients with chronic lymphocytic leukemia. These results suggest that variable region genes of RFs are highly conserved and that YES8c V(H), as well as V(K), may be identical to heavy and light chains expressed during early B cell development.