The IGH locus relocalizes to a “recombination compartment” in the perinucleolar region of differentiating B-lymphocytes

The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events...

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Published inOncotarget Vol. 8; no. 25; pp. 40079 - 40089
Main Authors Pichugin, Andrey, Iarovaia, Olga V., Gavrilov, Alexey, Sklyar, Ilya, Barinova, Natalja, Barinov, Aleksandr, Ivashkin, Evgeny, Caron, Gersende, Aoufouchi, Said, Razin, Sergey V., Fest, Thierry, Lipinski, Marc, Vassetzky, Yegor S.
Format Journal Article
LanguageEnglish
Published United States Impact journals 20.06.2017
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ISSN1949-2553
1949-2553
DOI10.18632/oncotarget.16941

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Abstract The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci. Our observations are consistent with the proposal that these IGH gene rearrangements take place in a specific perinucleolar "recombination compartment" where AID could be sequestered thus limiting the extent of its potentially deleterious off-target effects.
AbstractList The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci. Our observations are consistent with the proposal that these IGH gene rearrangements take place in a specific perinucleolar "recombination compartment" where AID could be sequestered thus limiting the extent of its potentially deleterious off-target effects.
The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci. Our observations are consistent with the proposal that these IGH gene rearrangements take place in a specific perinucleolar "recombination compartment" where AID could be sequestered thus limiting the extent of its potentially deleterious off-target effects.The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci. Our observations are consistent with the proposal that these IGH gene rearrangements take place in a specific perinucleolar "recombination compartment" where AID could be sequestered thus limiting the extent of its potentially deleterious off-target effects.
Author Lipinski, Marc
Sklyar, Ilya
Fest, Thierry
Ivashkin, Evgeny
Gavrilov, Alexey
Pichugin, Andrey
Razin, Sergey V.
Caron, Gersende
Vassetzky, Yegor S.
Iarovaia, Olga V.
Barinova, Natalja
Barinov, Aleksandr
Aoufouchi, Said
AuthorAffiliation 1 UMR8126, CNRS, Université Paris Sud Paris Saclay, Institut Gustave Roussy, Villejuif, France
2 Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia
6 UMR8200 CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France
8 Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia
3 LIA 1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France
4 Department of Experimental Neurocytology, Research Center of Neurology, Branch of Brain Research, Moscow, Russia
7 Moscow State University, Moscow, Russia
5 INSERM U1236, CHU de Rennes, Université Rennes 1, Rennes, France
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Keywords differentiation
recombination
chromatin
Chromosome Section
immunoglobulin genes
CHROMATIN
Differentiation
Language English
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Snippet The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and...
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StartPage 40079
SubjectTerms B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Cancer
Cell Differentiation - immunology
Cell Line, Tumor
Cell Nucleolus - immunology
Cell Nucleolus - metabolism
Cells, Cultured
Cytidine Deaminase - immunology
Cytidine Deaminase - metabolism
Germinal Center - cytology
Germinal Center - immunology
Germinal Center - metabolism
Humans
Immunoglobulin Class Switching - genetics
Immunoglobulin Class Switching - immunology
Immunoglobulin Heavy Chains - genetics
Immunoglobulin Heavy Chains - immunology
Immunoglobulin Heavy Chains - metabolism
Immunology
In Situ Hybridization, Fluorescence - methods
Life Sciences
Lymphocyte Activation - immunology
Microscopy, Confocal
Research Paper: Chromosome
Somatic Hypermutation, Immunoglobulin - genetics
Somatic Hypermutation, Immunoglobulin - immunology
Title The IGH locus relocalizes to a “recombination compartment” in the perinucleolar region of differentiating B-lymphocytes
URI https://www.ncbi.nlm.nih.gov/pubmed/28445143
https://www.proquest.com/docview/1892725860
https://univ-rennes.hal.science/hal-01560456
https://pubmed.ncbi.nlm.nih.gov/PMC5522243
Volume 8
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