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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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Journal ArticleDOI

Selective Usage of VH Genes in Adult Human B Lymphocyte Repertoires

TL;DR: The data show that V‐region mediated selection participates in shaping the peripheral antibody repertoire in healthy adults and does not correlate with the genomic complexity of human VH genes.
Journal ArticleDOI

Bone marrow cells in X-linked agammaglobulinemia express pre-B-specific genes (lambda-like and V pre-B) and present immunoglobulin V-D-J gene usage strongly biased to a fetal-like repertoire.

TL;DR: The data suggest that the XLA defect does not alter V-D-J rearrangements nor the expression of mu, lambda-like, and V pre-B transcripts and most likely results in a poor efficiency of some critical steps of the B cell maturation.
Journal ArticleDOI

Characterization of the immunoglobulin heavy chain complementarity determining region (CDR)-III sequences from human B cell precursor acute lymphoblastic leukemia cells.

TL;DR: The data showed the possibility of somatic mutation at relapse, in addition to developmentally regulated rearrangement of the immunoglobulin gene at the stage of B cell precursors, in order to elucidate the organization of CDR-III in B cell Precursors.
Journal ArticleDOI

Structural characterization of broadly neutralizing human monoclonal antibodies against the CD4 binding site of HIV-1 gp120

TL;DR: These studies suggest that there is no absolute restriction in the use of V region germline genes and form the foundation for understanding the humoral immune response to the CD4-binding site of gp120.
Journal ArticleDOI

Anti-DNA and anti-platelet specificities of SLE-derived autoantibodies: evidence for CDR2H mutations and CDR3H motifs.

TL;DR: Assessment of VH and VL region sequences of 10 human hybridoma anti-DNA autoantibodies derived from peripheral blood lymphocytes of different origins suggests that antigenic and functional differences between SLE-derived and normal-derived platelet-binding anti- DNA autoantibia may be due to antigen-selected mutations in the CDR2H and specific amino acid motifs in theCDR3H.
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