A uniform deleting element mediates the loss of κ genes in human B cells

Human immunoglobulin light-chain genes become rearranged in an ordered fashion during pre-B-cell development such that rearrangement generally occurs in κ genes before λ genes (refs 1,2). This ordered process includes an unanticipated deletion of the constant κ (Cκ) gene and κ enhancer sequence which precedes λ rearrangement1–4, and the site of this deletional recombination was located 3′ to the joining ( Jκ) segments in 75% of cases studied. We have now characterized the recombinational element responsible for this event on three separate alleles and found them to be identical. This κ-deleting element recombined site-specifically with a palindromic signal (CACAGTG) located in the Jκ–Cκ intron. All losses of Cκ genes in other human B cells were mediated by this determinant, including the 25% of instances when this element recombined with sequences 5′ to Jκ. In contrast, the κ-deleting element remained in its germline form on all successful κ-producing alleles. Moreover, κ loss is an evolutionary conserved event, as the κ-deleting element appears to be the human homologue of the murine RS sequence5. Our results suggest that this element may help ensure isotypic and allelic exclusion of light chains and may be involved in the ordered use of human light-chain genes.