Identification of a new human V lambda gene family--V lambda X.

Abstract

Although approximately 40% of Ig light chains in human sera are of the Ig lambda isotype, until recently very little was known about the human Ig lambda gene locus. The genomic structure of the Ig lambda C region has been determined and consists of seven tandemly organized J-C lambda segments. The structure of the region containing the Ig lambda V gene segments is less well defined. Based on amino acid and nucleotide sequence homologies, the V lambda gene segments isolated have been grouped into nine families. Here we report on the isolation of a V lambda gene from the functional rearrangement of a human B lymphoma cell line that has less than 71% nucleotide sequence and 57% deduced amino acid sequence homology to any known V lambda gene. According to the current classification schemes, this gene does not belong to any existing V lambda family. Thus we suggest that this gene belongs to a new V lambda family, V lambda X. The genomic counterpart of the rearranged V lambda gene, and a second member of the family were isolated. The second member is a pseudogene. Southern analysis suggests that the V lambda X family is a small family. The functional V lambda X gene has a consensus heptamer and a nonamer that differs at two sites from the consensus recombination signal sequence. The promoter region contains a consensus TATA box and an octamer that diverge from the consensus sequence by two base pairs.