Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus.
Jeffrey E. Berman,S. J. Mellis,Roberta R. Pollock,Cassandra L. Smith,Heikyung Suh,B. Heinke,C. Kowal,Urvashi Surti,Leonard Chess,C. R. Cantor +9 more
TLDR
The first report of the physical linkage of the variable and constant loci of a human Ig gene family is provided by demonstrating that the most proximal known human VH segments lie within 100 kb of the constant region locus.Abstract:
We present a detailed analysis of the content and organization of the human immunoglobulin VH locus. Human VH genes representing five distinct families were isolated, including novel members belonging to two out of three of the known VH gene families (VH1 and VH3) as well as members of three new families (VH4, VH5, and VH6). We report the nucleotide sequence of 21 novel human VH genes, many of which belong to the three new VH gene families. In addition, we provide a preliminary analysis of the organization of these gene segments over the full extent of the locus. We find that the five multi-segment families (VH1-5) have members interspersed over nearly the full 1500-2000 kb of the VH locus, and estimate that the entire heavy chain locus covers 2500 kb or less. Finally, we provide the first report of the physical linkage of the variable and constant loci of a human Ig gene family by demonstrating that the most proximal known human VH segments lie within 100 kb of the constant region locus.read more
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Immunoglobulin heavy-chain variable region polymorphisms and multiple-sclerosis susceptibility
TL;DR: The data are consistent with the IGVH locus exerting a minor effect perhaps by interacting with other loci to influence MS susceptibility or with genetic heterogeneity and a role for this complex in a subgroup of patients.
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Structural Analysis of VH4–21 Encoded Human IgM Allo‐ and Autoantibodies Against Red Blood Cells
TL;DR: In both groups of antibodies the region encoded by the VH4–21 segment can be found in germline configuration at the amino‐acid level indicating that other V‐gene structures, i.
Journal ArticleDOI
A Human Anti-Cardiolipin Autoantibody is Encoded by Developmentally restricted Heavy and Light Chain Variable Region Genes
Katherine A. Siminovitch,Virginia Misener,Pak C. Kwong,Pei-Ming Yang,Carl A. Laskin,Ewa Cairns,David A. Bell,Laurence A. Rubin,Pojen P. Chen +8 more
TL;DR: It is reported that the heavy and light chain V genes of an anti-cardiolipin antibody derived from a healthy individual display 99% nucleotide sequence homology with V genes expressed in early B cell ontogeny.
Journal ArticleDOI
Molecular approaches to the study of human B-cell and (auto)antibody repertoire generation and selection.
TL;DR: It is found that the repertoire of adult blood IgM-bearing B cells contains a high proportion of B lymphocytes that express extensively mutated VH genes, and somatically-mutated variants of particular VH and VL genes that, in germline configuration, are frequently found in the early B-cell repertoire and in natural autoantibodies, encode pathogenic IgG autoantIBodies characteristic of human SLE.