V-LAMBDA AND J-LAMBDA-C-LAMBDA GENE SEGMENTS OF THE HUMAN IMMUNOGLOBULIN-LAMBDA LIGHT CHAIN LOCUS ARE SEPARATED BY 14 KB AND REARRANGE BY A DELETION MECHANISM

We have cloned a region of 124 kb of the human immunoblogulin lambda-light chain locus on chromosome 22 encompassing seven V-lambda and seven J-C-lambda gene segments. No further C-lambda gene segment was found in a region of 35 kb downstream of C-lambda-7, which encodes the Ke+Oz- isotype. The C-lambda proximal V-lambda gene segment V-lambda-III.1 is located 14.5 kb upstream of C-lambda-1. The five sequenced V-lambda genes have the same transcriptional orientation as the J-C-lambda gene segments which is likely to be true for the majority of the V-lambda gene segments in the human lambda-locus and which suggests a deletion mechanism for DNA rearrangement. This is supported by hybridization of V-lambda gene probes to germ-line and rearranged DNA from lambda-light chain-producing cell lines. Sequences of 23 cDNA clones allow to establish a V-lambda subgroup classification based on nucleic acid sequence data and an estimate of the J-C-lambda usage.