Nonproductive kappa immunoglobulin genes: Recombinational abnormalities and other lesions affecting transcription, RNA processing, turnover, and translation

Six nonproductive kappa immunoglobulin genes (κ^- alleles) were cloned and sequenced. The structural abnormalities discerned from sequence analysis were correlated with functional lesions at the level of transcription, RNA processing, turnover, and translation. Four κ^- alleles, three containing V(κ) genes and one not, are transcribed at normal or even greater than normal rates, the defects in these genes being expressed at various posttranscriptional levels. The other two κ^- alleles, both of which lacked V genes, exhibited greatly depressed yet clearly detectable transcriptional activity. These results are consistent with a hierarchical relationship between enhancer and promoter elements in which the enhancer establishes transcriptional competence at the κ locus and the promoter (or pseudopromoter) determines the relative level of transcriptional activity. One of the structural abnormalities discovered in this study, a large deletion which removes the entire J(κ) region, also provides new insight into the mechanism of VJ and VDJ recombination.