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 _κIII, J_κ2, V_H1, J_H4, 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_κIII germline gene (Humkv325). The YES8c heavy chain variable region gene was most closely related to the V_H1 gene of the restricted human fetal repertoire, designated 51p1, and also to 3 rearranged V_H1 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 Vκ, may be identical to heavy and light chains expressed during early B cell development.