GENERATION OF IMMUNOGLOBULIN LIGHT-CHAIN GENE DIVERSITY IN RAJA-ERINACEA IS NOT ASSOCIATED WITH SOMATIC REARRANGEMENT, AN EXCEPTION TO A CENTRAL PARADIGM OF B-CELL IMMUNITY

In all vertebrate species examined to date, rearrangement and somatic modification of gene segmental elements that encode portions of the an tigen-combining sites of immunoglobulins are integral components of th e generation of antibody diversity. In the phylogenetically primitive cartilaginous fishes, gene segments encoding immunoglobulin heavy and light chain loci are arranged in multiple clusters, in which segmental elements are separated by only 300-400 bp. In some cases, segmental e lements are joined in the germline of nonlymphoid cells (joined genes) . Both genomic library screening and direct amplification of genomic D NA have been used to characterize at least 89 different type I light c hain gene clusters in the skate, Raja. Analyses of predicted nucleotid e sequences and predicted peptide structures are consistent with the d istribution of genes into different sequence groups. Predicted amino a cid sequence differences are preferentially distributed in complementa rity-determining versus framework regions, and replacement-type substi tutions exceed neutral substitutions. When specific germline sequences are related to the sequences of individual cDNAs, it is apparent that the joined genes are expressed and are potentially somatically mutate d. No evidence was found for the presence of any type I light chain ge ne in Raja that is not germline joined. The type I light chain gene cl usters in Raja appear to represent a novel gene system in which combin atorial and junctional diversity are absent.