Transcription and diversity of immunoglobulin lambda chain variable genes in the rat.

In order to determine the extent of the repertoire of the immunoglobulin light chain V-region locus (Igl-V) in the laboratory rat (Rattus norvegicus), we constructed a specifically primed cDNA library from lipopolysaccharide-stimulated DA strain rat spleens. The library was screened with a rat Igl-C2-specific probe, and 33 clones containing identifiable V regions were sequenced, of which 19 sequences are presented here. In addition to one sequence (Igl-V1) which was already known, and is closely related to the two known mouse V lambda gene segments, clones encoding representatives of three new, distantly related, rat Igl-V subfamilies were found, namely Igl-V2, Igl-V3, and Igl-V4. At least two of these sub-families, Igl-V2 and Igl-V3, contain multiple members as well as restriction fragment length polymorphism variants, indicating the presence of at least 10-15 Igl-V gene segments (including some pseudogenes) in the rat genome. An additional ten clones contained no rearranged V region, although they showed a correct J-C splice, suggesting the presence of cryptic transcriptional promoters between J lambda and the 3'-most Igl-V gene segment. Phylogenetic tree reconstruction based on amino acid sequence alignments showed at least three of the four rat Igl-V sequences clustering with distinct human Igl-V genes. Thus, although rats express lambda-bearing Ig at levels no higher than mice, the rat Igl-V locus is considerably more complex than that of laboratory mice, and its diversity reflects the products of gene duplications which predate the time of primate/rodent divergence.