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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Transgenic Non-Human Animals For Producing Chimeric Antibodies
Nils Lonberg,Robert M. Kay +1 more
TL;DR: In this article, a transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity are described.
Book ChapterDOI
Physical maps of the mouse and human immunoglobulin-like loci.
TL;DR: This chapter groups these gene families as immunoglobulin-like loci, because they are molecular families that are constructed based on the immunoglobeulin homology unit.
Journal ArticleDOI
Molecular evolution of the human immunoglobulin E response: high incidence of shared mutations and clonal relatedness among epsilon VH5 transcripts from three unrelated patients with atopic dermatitis.
TL;DR: It is hypotheses that the V regions of immunoglobulin E-bearing B cells have accumulated "selectively neutral" mutations over extended periods of clonal expansion, resulting in unusual R/S ratios and the molecular characteristics of the epsilon VH regions in atopic dermatitis may be representative of antigens that recurrently or chronically stimulate the immune system.
Journal ArticleDOI
Nucleotide sequence analysis of rheumatoid factors and polyreactive antibodies derived from patients with rheumatoid arthritis reveals diverse use of VH and VL gene segments and extensive variability in CDR-3.
Virginia Pascual,K Victor,I. Randen,Keith Thompson,M. Steinitz,Øystein Førre,S M Fu,Jacob B. Natvig,J D Capra +8 more
TL;DR: The heavy and light chain nucleotide sequences of 17 monoreactive and polyreactive rheumatoid factors largely derived from the inflamed synovial tissue of two patients with rheumatic arthritis are described.
Journal ArticleDOI
VH gene usage is multiple myeloma: complete absence of the VH4.21 (VH4-34) gene.
Matthew Rettig,Robert Vescio,Jin Cao,C. H. Wu,Jong C. Lee,Eugene Han,Melina DerDanielian,Roland Newman,Charlie Hong,Alan Lichtenstein,James R. Berenson +10 more
TL;DR: The reverse transcriptase-polymerase chain reaction based technique concludes that the VH gene usage in MM is unique compared with other malignant and nonmalignant B-cell populations, and the physiologic process of clonal deletion functions to remove clones that have rearranged VH genes (VH4.21) capable of expressing antibodies, which recognize self-antigens, may help to partially explain the paucity of autoimmune phenomena in MM.