IDENTIFICATION AND CHARACTERIZATION OF A FUNCTIONAL HUMAN IG V-LAMBDA-VI GERMLINE GENE

We have isolated from a human genomic library a potentially functional and distinctive germline gene, designated IGLV6S1, that encodes for l ight chains of the V-lambda VI subgroup. An identical germline gene wa s cloned from fibroblasts obtained from a patient with light-chain-ass ociated amyloidosis (AL amyloidosis) whose serum and urine contained, respectively, a monoclonal IgG lambda VI protein and a lambda VI Bence Jones protein. Isolation and characterization of cDNA cloned from the patient's bone marrow-derived monoclonal plasma cells revealed that t he nucleotide and predicted protein sequences of the rearranged gene w ere similar to 95% and similar to 90% homologous to those of the germl ine gene, respectively. The finding that the transcriptional start sit e for lambda VI RNA synthesis was located upstream of the putative TAT A-box promoter, rather than downstream as found for the V-lambda II su bgroup, implies that a different transcriptional machinery controls th e expression of the human V-lambda VI-gene family.