The human immunoglobulin x locus. Characterization of the duplicated O regions

Abstract

Two large regions of the human immunoglobulin kappa locus, the so-called O regions, have been characterized on cosmid and phage lambda clones. The two regions are very similar but not identical duplicates belonging to the C kappa proximal (p) and the distal (d) copies of the kappa locus. The Op and Od regions comprise contigs of 90 and 120 kb, respectively, and contain 20 V kappa genes and pseudogenes which have been sequenced. Three pairs of V kappa genes were found to be practically identical in the duplicates while allotypic differences, at least for two of the genes, are considerable. The similarities between the duplicate genes may be related to the fact that the two copies of the kappa locus are arranged in a palindrome-like fashion with the 5' sides of the O regions pointing towards each other (C kappa J kappa B Lp Ap Op-Od Ad Ld). This may have contributed to equalizing the sequences. Beyond Op and Od no further V kappa genes were found within about 80 kb. Instead, repetitive DNA sequences have been localized there, the structures of which suggest that they may have been involved in the evolution of the V kappa gene-containing regions. The V kappa pseudogene containing W regions, that had been transposed in evolution from the short to the long arm of chromosome 2 by a pericentric inversion, may have been derived from the O regions according to structural homologies between defined sections of the O and W regions.

The Vχ genes of the L regions and the repertoire of Vχ gene sequences in the human germ line

“…1. The 5', 3' polarity of L13 is the same as that of its neighbors L12 and B1 and, therefore, opposite to that of B2 and B3 [S]. sequenced in subclones of cos 138 and in the yeast artificial chromosome (YAC) clone 32C6.…”

Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.

“…Among them, lv 1 17 is identical to the L chain of the Kim4.6 anti-DNA antibody and lvi LI encodes the L chain of the LI IgG RF (Table IV) (Table IV). Of the four, the 012 VK 1 gene apparently encodes the 15A anti-I cold agglutinin (62,63). To counter the possibility that the difference between the V gene utilization patterns of H and L chains in anti-pathogen antibodies is due to limited information on VL gene usage, Table IV antigens, and thus are expanded to form the "preinfection" (or "natural") antibody repertoire.…”

Vχ gene segments rearranged in chronic lymphocytic leukemia are distributed over a large portion of the Vχ locus and do not show somatic mutation

“…Sequences 26 to 28 are similarly derived from either of the two copies of humkv328 [35,36]. Our sequence 10 differed by two amino acids from the sequence of 02-012, but it is in fact identical to an allelic variant of 0 1 2 which has recently been reported [34].…”

“…3): this means that in all these cases there are neither expressed nor silent mutations. Some sequences have identical coding regions in both Jx-proximal and Jx-distal sections of the 1ocus.To indicate this we have used the nomenclature of Pargent et al [34]. Sequences 10 to 14 may come from either 0 2 or 012, sequences 15 to 17 from either 0 8 or 0 1 8 and sequences 19 to 21 from either A3 or A19.…”

“…The sequences of the oligonucleotide primers are not included in the sequences presented here. All prototype sequences were obtained from [23] apart from A20 [32], A3-Al9 [241, humkv325 [25], 08-018 [33], 02-012 [34] and humkv328 [35,36]. The numbering of amino acids is according to Kabat et al [23].…”