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 in | Oncotarget Vol. 8; no. 25; pp. 40079 - 40089 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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20.06.2017
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ISSN | 1949-2553 1949-2553 |
DOI | 10.18632/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. |
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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 |
AuthorAffiliation_xml | – name: 7 Moscow State University, Moscow, Russia – name: 1 UMR8126, CNRS, Université Paris Sud Paris Saclay, Institut Gustave Roussy, Villejuif, France – name: 4 Department of Experimental Neurocytology, Research Center of Neurology, Branch of Brain Research, Moscow, Russia – name: 2 Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia – name: 6 UMR8200 CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France – name: 3 LIA 1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France – name: 8 Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia – name: 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 |
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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 |
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