Nonproductive Kappa Immunoglobulin Genes: Recombinational Abnormalities and Other Lesions Affecting Transcription, RNA Processing, Turnover, and Translation

Abstract

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.