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

2017; Impact Journals LLC; Volume: 8; Issue: 25 Linguagem: Inglês

10.18632/oncotarget.16941

1949-2553

Andrey Pichugin, Olga V. Iarovaia, Alexey A. Gavrilov, I. V. Sklyar, Natalja Barinova, Aleksandr Barinov, Evgeny Ivashkin, Gersende Caron, Saïd Aoufouchi, Sergey V. Razin, Thierry Fest, Marc Lipinski, Yegor Vassetzky,

Immune Cell Function and Interaction

// Andrey Pichugin 1,3,8,* , Olga V. Iarovaia 1,2,3,* , Alexey Gavrilov 2,3 , Ilya Sklyar 1,2,3 , Natalja Barinova 1,3 , Aleksandr Barinov 3 , Evgeny Ivashkin 1,3,4 , Gersende Caron 5 , Said Aoufouchi 6 , Sergey V. Razin 2,3,7 , Thierry Fest 5 , Marc Lipinski 1,3 and Yegor S. Vassetzky 1,3,7 1 UMR8126, CNRS, Université Paris Sud Paris Saclay, Institut Gustave Roussy, Villejuif, France 2 Institute of Gene Biology, Russian Academy of Sciences, Moscow, 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 5 INSERM U1236, CHU de Rennes, Université Rennes 1, Rennes, France 6 UMR8200 CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France 7 Moscow State University, Moscow, Russia 8 Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia * These authors have contributed equally to this work Correspondence to: Yegor S. Vassetzky, email: // Keywords : immunoglobulin genes, chromatin, recombination, differentiation Received : March 22, 2017 Accepted : March 29, 2017 Published : April 07, 2017 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.