Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange

Tina Østergaard Hansen, Anders Blaabjerg Lange, Torben Barington

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B cells from 110 healthy adult donors. We found that DJH rearrangements and nonproductive VHDJH rearrangements share many features but differ significantly in their use of D genes and propensity for somatic hypermutation. In D to JH gene rearrangements, the D genes proximal to the JH locus are used more frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus.

OriginalsprogEngelsk
TidsskriftJournal of Immunology
Vol/bind194
Udgave nummer3
Sider (fra-til)973-82
ISSN0022-1767
DOI
StatusUdgivet - 1. feb. 2015

Citer dette

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title = "Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange",
abstract = "Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B cells from 110 healthy adult donors. We found that DJH rearrangements and nonproductive VHDJH rearrangements share many features but differ significantly in their use of D genes and propensity for somatic hypermutation. In D to JH gene rearrangements, the D genes proximal to the JH locus are used more frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus.",
keywords = "B-Lymphocytes, Gene Order, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Genetic Loci, High-Throughput Nucleotide Sequencing, Humans, Immunoglobulin Heavy Chains, Reproducibility of Results, Somatic Hypermutation, Immunoglobulin, V(D)J Recombination",
author = "Hansen, {Tina {\O}stergaard} and Lange, {Anders Blaabjerg} and Torben Barington",
note = "Copyright {\circledC} 2015 by The American Association of Immunologists, Inc.",
year = "2015",
month = "2",
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doi = "10.4049/jimmunol.1401443",
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Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange. / Hansen, Tina Østergaard; Lange, Anders Blaabjerg; Barington, Torben.

I: Journal of Immunology, Bind 194, Nr. 3, 01.02.2015, s. 973-82.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange

AU - Hansen, Tina Østergaard

AU - Lange, Anders Blaabjerg

AU - Barington, Torben

N1 - Copyright © 2015 by The American Association of Immunologists, Inc.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B cells from 110 healthy adult donors. We found that DJH rearrangements and nonproductive VHDJH rearrangements share many features but differ significantly in their use of D genes and propensity for somatic hypermutation. In D to JH gene rearrangements, the D genes proximal to the JH locus are used more frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus.

AB - Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B cells from 110 healthy adult donors. We found that DJH rearrangements and nonproductive VHDJH rearrangements share many features but differ significantly in their use of D genes and propensity for somatic hypermutation. In D to JH gene rearrangements, the D genes proximal to the JH locus are used more frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus.

KW - B-Lymphocytes

KW - Gene Order

KW - Gene Rearrangement, B-Lymphocyte, Heavy Chain

KW - Genetic Loci

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Immunoglobulin Heavy Chains

KW - Reproducibility of Results

KW - Somatic Hypermutation, Immunoglobulin

KW - V(D)J Recombination

U2 - 10.4049/jimmunol.1401443

DO - 10.4049/jimmunol.1401443

M3 - Journal article

VL - 194

SP - 973

EP - 982

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -