Evolutionary dynamics of the human immunoglobulin κ locus and the germline repertoire of the Vκ genes

Abstract

We have determined the entire nucleotide sequence of the human immunoglobulin κlocus, comprising a total of 1,010,706 nucleotides. The 76 Vκgenes found by a hybridization‐based approach and their classification in 7 families were confirmed. A Vκorphon located near the locus was also sequenced. In addition, we identified 55 novel Vκrelics and truncated pseudogenes, which establish 5 new families. Among these 132 Vκgenes, 46 have open reading frames. According to the databases and the literature, 32 unique Vκgenes and 5 identical gene pairs form VJ‐joints, 27 unique genes and 4 gene pairs are transcribed, and 25 unique genes and 4 gene pairs produce functional proteins. The Vκgene locus contains a 360‐kb inverted duplication, which harbors 118 Vκgenes. A comparison of the duplicated Vκgenes suggests positive selection on the complementarity‐determining regions of the duplicated genes by point mutations. The entire duplication unit was divided into 13 blocks, each of which has its distinct nucleotide sequence identity to its duplication counterpart (98.1 – 99.9 %). An inversion‐mediated mechanism is suggested to generate the high‐homology blocks. Based on the homology blocks and the mutation rates, the inverted duplication is assumed to have taken place ∼ 5 million years ago. An orphon Vκgene near the κlocus and a cluster of five Vκorphons on chromosome 22 have no counterparts within the κlocus. This suggests possible mechanisms of the transposition of orphon Vκgenes.

B cell receptor light chain repertoires show signs of selection with differences between groups of healthy individuals and SLE patients

“…Thus, the initial repertoire diversity is due to combinatorial association of H-chains and L-chains as well as combinatorial joining of V, D and J gene segments. (Kawasaki et al, 2001; Kawasaki et al, 1997; Matsuda et al, 1998). Additional diversity arises at the junction of V, D and J gene segments by N-nucleotide additions, P-nucleotide additions and nibbling (Weigert et al, 1980; Wu and Kabat, 1970).…”

The κB transcriptional enhancer motif and signal sequences of V(D)J recombination are targets for the zinc finger protein HIVEP3/KRC: a site selection amplification binding study

“…To further determine the physiological significance of KRC's DNA binding, we compared the datasets with known endogenous RSSs of Ig and TCR loci. The mouse TCR αchain J gene segments (TCRAJ) and the human Igκ light chain genes (IgVκ) were analyzed, taking advantage of the fact that both loci have been sequenced and the location and sequence of their RSSs have been characterized [45,46]. Of the 97 IgVκ gene segments listed, 42 (43%) have a nonamer, a heptamer or both matching a sequence within the datasets (Figure 15).…”

“…The KRC-bound sequences were compared to known RSS sequence in the murine TCR-alpha genes and the human immunoglobulin heavy chain genes, the loci of which have been fully sequenced [45,46]. Individual sequences in the training sets were compared manually with (A) RSS nonamers or (B) RSS hepamers defined in of the human Ig variable region gene segments of κ light chain (Table 1 of [45]) and the mouse TCRAJ gene segments (Fig. 2 of [46]).…”

“…Sequence in the KRC fusion protein-bound oligonucleotides overlapped with heptamer, nonamer, or both in the RSS of 43.3% of human IgVκ genes and in 33.9% of murine TCRAJ genes. These calculations include only the IgVκ [45] and TCRAJ genes [46] which contain a nonamer, a heptamer, or both.…”

Antibody repertoires in infants and adults: effects of T-independent and T-dependent immunizations

“…The human VK locus is partially duplicated, such that many VK segments located proximal to the K constant region have identical or near-identical sister genes located distally and in the opposite transcriptional orientation [38]. The homologue of the A2 gene is A18, which has five known alleles (a-e), of which four are functional (b-e) and have identical translated amino acid sequences that differ from A2 by 4 amino …”