Functional Significance and Evolutionary Development of the 5'-terminal Regions of Immunoglobulin Variable-region Genes

The 5'-terminal sequence of the kappa light-chain gene expressed in MPC11 plasmacytoma cells was definitively determined by analysis of both the kappa mRNA and the gene from which it is transcribed. The distance between the cap site and the translation initiation codon is only 3 nucleotides, and in a minor variant only 2 nucleotides, considerably less than that found in other species of nucleus-derived mRNA. S1 nuclease protection experiments with MPC11 nuclear RNA indicate that the cap sites are coincident with the transcriptional start sites, suggesting that the 5'-terminal heterogeneity is caused by imprecision in transcriptional initiation. A comparison of the 5'-terminal structure of the MPC11 V kappa gene with that of several other V genes indicates that the length of the first exon, which is composed of the 5' untranslated region which is composed of the 5' untranslated region and a sequence encoding most of the signal peptide, is highly conserved. Within this set of examples, the 5' untranslated region varies from 3 to 33 nucleotides, and the signal-peptide-coding block from 46 to 76 nucleotides. This analysis has also provided insight into the genetic origins for two anomalous properties of the MPC11 light chain.