Biased Immunoglobulin Light Chain Gene Usage in the Shark

This study of a large family of kappa L chain clusters in nurse shark completes the characterization of its classical Ig gene content (two H chain isotypes, mu and omega, and four L chain isotypes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over an similar to 500-bp interval, and functional clusters are widely separated by at least 100 kb. Six out of similar to 39 kappa clusters are prerearranged in the germline (germline joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, nonproductive, and sterile transcripts of the kappa clusters compared with the other three L chain isotypes. kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and nonproductive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is nonrandom. Although both split and germline-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing.