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Open AccessJournal ArticleDOI

Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus.

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.

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"Primatization" of recombinant antibodies for immunotherapy of human diseases: a macaque/human chimeric antibody against human CD4.

TL;DR: It is shown that cynomolgus macaques are phylogenetically distant enough to respond against conserved human antigens, and a human/monkey chimeric anti-CD4 antibody with an apparent affinity of 3.2 × 10−11 M and exhibits potent immunosuppressive properties in vitro.
Journal ArticleDOI

Clonal expansion in follicular lymphoma occurs subsequent to antigenic selection.

TL;DR: Comparison of the GL V gene sequence to a consensus of MT FL V gene sequences revealed 42 mutations, demonstrating that malignant clonal expansion occurred subsequent to the activation of somatic mutation, presumably in the malignant follicle.
Journal ArticleDOI

The complete nucleotide sequences of the heavy chain variable regions of six monospecific rheumatoid factors derived from Epstein-Barr virus-transformed B cells isolated from the synovial tissue of patients with rheumatoid arthritis. Further evidence that some autoantibodies are unmutated copies of germ line genes.

TL;DR: This study isolated and sequenced the VH regions of six monoclonal RF derived from the synovial membranes of two patients with rheumatoid arthritis and one with the juvenile polyarticular form of the disease and found that different JH gene segments may contribute to RF specificity.
Journal ArticleDOI

Immunoglobulin heavy chain variable region family usage is independent of tumor cell phenotype in human B lineage leukemias.

TL;DR: Since blast cells in acute lymphoblastic leukaemia do not express functional immunoglobulin, it is inferred that the tumor cell‐associated VH family repertoire is determined through antigen‐independent mechanisms.
Journal ArticleDOI

Cell cycle dependent chromosomal movement in pre-mitotic human T-lymphocyte nuclei.

TL;DR: It is demonstrated that dynamic chromosome rearrangements occur in non-mitotic nuclei during the cell cycle, as well as in a small subset of G2 nuclei approaching mitosis.
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