Immunoglobulin κ light-chain diversity in rabbit is based on the 3′ length heterogeneity of germ-line variable genes

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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 mechanisms1–6. The κ system in mouse and human consists of 50–100 Vκ segments associated with a cluster of four or five functional Jκ segments, located 2.5 kilobases (kb) 5′ to a single Cκ gene7–10. The third hypervariable region (CDR3), which is part of the antibody combining site, is usually nine amino acids long in human and mouse κ chains. It is encoded by the last seven codons of the Vκ segment and the first two of the Jκ segment, one codon sometimes being added or deleted between V and J by junctional variation2. In the rabbit, the Cκ1 gene which encodes the major isotype11–14, is associated with a cluster of five Jκ segments, only one of which seems to be functional11, thus significantly decreasing the combinatorial potential. However, amino acid sequence comparison has revealed extensive heterogeneity in the length of rabbit CDR3 (ref. 15), suggesting the existence of a D segment analogous to that in the heavy-chain system. We show here that rabbit Vκ genes have several additional nucleotides at their 3′ ends. Thus, even with a single functional Jκ segment, high CDR3 diversity can be generated based on the length heterogeneity of Vκ germ-line segments and their greater length, which might leave scope for an increased junctional deletion.