Characterization of four homologous L chain variable region genes that are related to 6B6.6 idiotype positive human rheumatoid factor L chains.

Abstract

A significant proportion of monoclonal IgM rheumatoid factors (RF) from patients with mixed cryoglobulinemia express a KIIIa L chain-associated cross-reactive idiotype, termed 6B6.6. Previously, we reported the isolation from a patient with a monoclonal RF of a Vk gene, termed Humkv328, whose deduced amino acid sequence differs by three and seven residues from the L chains of the 6B6.6-positive RF Les and Pom, respectively. To further delineate the genetic basis of the 6B6.6 cross-reactive idiotype, we isolated from the same patient another Vk gene, termed Humkv329, which differs from kv328 by only three bases over a stretch of 1331 nucleotides sequenced. However, kv329 has a stop codon at amino acid position 94, and is thus a pseudogene. Therefore, we screened a second genomic library from an unrelated individual and isolated two potential function Vk genes (i.e., Humkv328h2 and Humkv328h5) which are highly homologous to Humkv328. All three potential functional Vk genes differ from each other by one to six bases over a 1331-bp stretch and all encode the same Vk region amino acid sequence. Among the six bases by which Humkv328h5 differs from Humkv328, two are in the conserved pentadecanucleotide region, which is known to be important in the regulation of k L chain transcription. In the future it will be important to ascertain the potential association of polymorphisms in the conserved pentadecanucleotide region with RF associated autoimmune and lymphoproliferative diseases.