Nonfunctional immunoglobulin light chain transcripts in two IgE-producing rat immunocytomas; implications for the allelic exclusion and transcription activation processes

Abstract

The rearrangement and expression of immunoglobulin light-chain genes have been studied in two IgE-producing immunocytomas, IR2 and IR162. In the IR2 tumor only one of the kappa-chain alleles is rearranged, expressing a full-length kappa-chain polypeptide. In IR162 one of the kappa-chain alleles is functionally rearranged, expressing a 1200-nucleotide (nt) long mRNA, which encodes a functional 23-kDal kappa-chain polypeptide. The second kappa-chain allele is aberrantly rearranged; i.e., a different V region is connected to a position that is located between the J cluster and the C kappa exon. Two mRNAs which are 750 and 850 nt are transcribed from the aberrantly rearranged allele, both of which appear to encode a 12-kDal polypeptide consisting of a signal sequence that is connected directly to the C region. The levels of expression from the two kappa-chain alleles are approximately the same, suggesting that no specific mechanism exists to suppress expression of a nonfunctional allele. The rat genome contains a single lambda-chain locus which includes two C-region exons. Although this locus remains in the germ-line configuration in the IR2 and the IR162 tumors, transcripts from the C lambda I and C lambda II regions were detected at a low level in both tumors. These transcripts were detected in RNA from the immunocytomas but not in rat liver RNA indicating that expression is tissue-specific. They lacked V-region sequences and resemble so-called sterile transcripts which are expressed at a low level from unrearranged mu- and kappa-chain genes.