title: Immunoglobulin kappa light-chain diversity in rabbit is based on the 3' length heterogeneity of germ-line variable genes.
abstract: Antibody diversity is generated by the combinatorial association of multiple distinct genetic segments (variable (V), joining (J) and diversity (D) light (L) and heavy (H) chains--VL, JL and VH, D, JH) and amplified somatically by three or four different mechanisms. The kappa system in mouse and human consists of 50-100 V kappa segments associated with a cluster of four or five functional J kappa segments, located 2.5 kilobases (kb) 5' to a single C kappa gene. The third hypervariable region (CDR3), which is part of the antibody combining site, is usually nine amino acids long in human and mouse kappa chains. It is encoded by the last seven codons of the V kappa segment and the first two of the J kappa segment, one codon sometimes being added or deleted between V and J by junctional variation. In the rabbit, the C kappa 1 gene which encodes the major isotype, is associated with a cluster of five J kappa segments, only one of which seems to be functional, thus significantly decreasing the combinatorial potential. However, amino acid sequence comparison has revealed extensive heterogeneity in the length of rabbit CDR3 , suggesting the existence of a D segment analogous to that in the heavy-chain system. We show here that rabbit V kappa genes have several additional nucleotides at their 3' ends. Thus, even with a single functional J kappa segment, high CDR3 diversity can be generated based on the length heterogeneity of V kappa germ-line segments and their greater length, which might leave scope for an increased junctional deletion.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D005796:Genes; D006720:Homozygote; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008099:Liver / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D010957:Plasmids; D011817:Rabbits; D013045:Species Specificity
chemical_list: D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D004247:DNA