Evolution of the immunoglobulin kappa light chain locus in the rabbit: evidence for differential gene conversion events.

Abstract

The rabbit Kc light chain gene family is characterized by the presence of two constant region (CQ) genes; the Cd gene encodes the constant region of the principal rabbit immunoglobulin light chain, the CK2 gene being not or very poorly expressed in domestic rabbits. There exist four major KI alleles (b4, b5, b6, and b9), which are unequally expressed in heterozygous rabbits at the K) locus. Here, we compare the nucleotide sequences of the joining (J) clusters of the K light chain gene (JK) linked to the b4K2 locus and to the b and b9 alleles at the K) locus. As for CK genes, there is evidence for intergenic conversion between the Jud and JK,2 clusters as well as maximum divergence in the expressedJ segments. The b9Jd cluster differs from its b4 counterpart in that two out of the five JK segments (Ji and J2) are expressed instead of only one. This implies that preferential expression of the b4 allele as compared to the b9 allele is not only correlated to the number of available Je pieces. The b9 J2 segment is functional in spite of the presence of a termination codon immediately upstream of its coding region. Two major structural differences were observed between the J-C intron sequences of the b9 and b4 alleles; namely a 160-base-pair deletion of an A+T-rich sequence in b9 (which also occurs in the K2 locus) and a 10-base-pair deletion plus some substitutions in the region corresponding to the mouse K intron activating element. These differences could underlie the lower transcriptional rate of the b9 allele.The rabbit immunoglobulin K light chain gene family constitutes an interesting model for the study of complex allele evolution and of the cis elements that control gene expression. In contrast to the situation in humans and mice, in domestic rabbits two K chain loci, K) and K2, encode the K chain bearing the nominal b allotype of the rabbit and the bas chain expressed in wild rabbits and in rabbits of the Basilea strain, respectively (1, 2).In mature B cells of rabbits heterozygous for the K) locus, the two alleles are unequally expressed. The following "pecking order" is observed: b4 > bS > b6 > b9 with a b4/b9 allelic ratio of 80:20 (3-6). These alleles are characterized by a high level of divergence at the protein level (ranging from 22 to 33% of divergence). Structural analysis of the corresponding genes has suggested that most of the differences have been generated by gene conversion (7). Another remarkable feature of the K) locus is that, at least in the case of the b4 allele, only one out of the five joining (J) segments of the K light chain (QJ) is functional (8, 9). The decrease in diversity that could result from this limited combinatorial potential is compensated for by an increased junctional variation during the V-J (V, variable) recombination because of nucleotide deletions in the JK segments and length heterogeneity of the VK germ-line segments (10). From nucleotide sequencing data of the human, mouse, and rabbit genes, a highly conserved region has been identified within the J-CK intro...

Sequence analysis of 0.4 megabases of the rabbit germline immunoglobulin kappa1 light chain locus

“…This suggests that the κ 1 locus spans about 0.65 Mb containing more than 100 V κ elements separated by spacer sequences averaging 6 kb in length. This estimate is consistent with previous observations (Akimenko et al. 1986; Currier et al.…”

Characterization and DNA sequence of the b6w2 allotype of the rabbit immunoglobulin kappa 1 light chain (b locus)

“…Also the two remaining amino acid differences are confined to the steric environment of a disulfide bond (i. e., the interchain bound at Cys214 between the L chain and the heavy chain). Different authors have in the past commented on a hypothetical role played by the extra interdomain bond on the one hand and by genetic recombination on the other, in processes underlying the unusual evolutionary dynamics of b locus polymorphism (van der Loo 1975;Landucci-Tosi et al 1976;van der Loo et al 1976;McCartney-Francis et al 1984;Akimenko et al 1986;Mariam6 et al 1987;Ayadi et al 1991). The observations reported here substantiate some of these speculations and, moreover, indicate that synergistic effects between such putative diversity enhancing factors can exist.…”

Dysfunction of chromosomal loop attachment sites: illegitimate recombination linked to matrix association regions and topoisomerase II.

“…In the rabbit system, a 160-bp stretch corresponding to the smallest deleted region from the primordial K2-chain gene (Fig. 3E) is missing from the Kl-chain gene in certain strains (49 …”