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Organization and expression of the lambda-like genes that contribute to the mu-psi light chain complex in human pre-B
Insights
The human lambda-like gene cluster contains three genes, with 14.1 being the only functional gene encoding the 22 kDa light chain surrogate. This finding reveals similarities in gene organization between lambda and lambda-like loci.
Area of Science:
- Immunogenetics
- Molecular Biology
- Human Genetics
Background:
- Lambda-like genes encode a polypeptide chain forming the mu-psi light chain complex in pre-B cells.
- The human lambda-like gene cluster comprises three genes: 14.1, 16.1, and F lambda 1.
Purpose of the Study:
- To characterize the human lambda-like gene cluster, including gene organization, mapping, and functional analysis.
- To identify the functional gene within the lambda-like cluster responsible for encoding the light chain surrogate.
Main Methods:
- Gene isolation from cosmid libraries.
- Chromosomal mapping of the lambda-like gene cluster.
- Transcript analysis in human fetal liver using hybridization and sequencing.
Main Results:
- The lambda-like gene cluster is located on chromosome 22, distal to the BCR gene.
- Gene organization is similar to lambda loci, with a three-exon gene upstream of tandemly organized J lambda-C lambda-like genes.
- Gene 14.1 is the sole functional gene, producing a full-length mRNA transcript encoding the 22 kDa light chain surrogate.
Conclusions:
- The 14.1 gene is the only functional gene within the human lambda-like cluster.
- The gene organization of lambda and lambda-like loci is conserved.
- Functional analysis of lambda-like genes is crucial for understanding B-cell development.
Abstract:
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.