ORGANIZATION AND EXPRESSION OF THE LAMBDA-LIKE GENES THAT CONTRIBUTE TO THE MU-PSI LIGHT CHAIN COMPLEX IN HUMAN PRE-B-CELLS

Lambda-like genes encode a polypeptide chain that associates with VpreB and mu-chain in the so-called mu-PSI-light chain complex specifically expressed in pre-B cells. In humans, the lambda-like gene cluster contains three genes, termed 14.1, 16.1, and F-lambda-1. The 14.1 gene contains three exons and was previously sequenced. The 16.1 and F-lambda-1 have been isolated from cosmid libraries. They both contain only the exons 2 and 3 that appear highly homologous to their 14.1 counterparts. The lambda-like gene cluster has been mapped on chromosome 22, close and distal to the BCR gene, in the order (14.1; F-lambda-1) and 16.1. Hybridization with the 14.1 exon 1 probe did not detect an equivalent on 16.1 and F-lambda-1 genes, but instead, only revealed the X6 gene, that was previously identified 5 kb upstream of the IGLC locus. It appears, therefore, that the gene organization of the lambda and lambda-like loci is strikingly similar, with a three-exon-containing gene 5' of a series of J-lambda-C-lambda or J-lambda-C-lambda-like tandemly organized genes. Analysis of the transcripts in a 8 week old human fetal liver clearly indicated that 14.1 was the only functional gene of the lambda-like cluster. Various forms of transcripts resulting from alternate splicing have been characterized. The major component consisted of a full-length (exons 1-2-3) mRNA, whereas a minor (1-3) transcript was identified. Only the full-length transcript could encode a functional polypeptide chain corresponding to the 22 kDa light chain surrogate.