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

Andrey Pichugin (1, 2) , Olga V. Iarovaia (3, 2) , Alexey Gavrilov (3) , Ilya Sklyar (3, 2) , Natalja Barinova (2) , Aleksandr Barinov , Evgeny Ivashkin , Gersende Caron (4, 5) , Said Aoufouchi (6) , Sergey V. Razin (3, 7) , Thierry Fest (8, 5) , Marc Lipinski (2) , Yegor S. Vassetzky (2)

1 SPbPU - Peter the Great St. Petersburg Polytechnic University
2 UMR8126 - Signalisation, noyaux et innovations en cancérologie
3 Institute of Gene Biology, Russian Academy of Sciences
4 Pôle biologie
5 MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer
6 CNRS UMR 8200 - Réparation de l’ADN
7 Faculty of biology
8 Service d’immunologie, de thérapie cellulaire et d’hématopoïèse

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.

Keywords: CHROMATIN; Chromosome Section; Differentiation; immunoglobulin genes; recombination

Domains: Life Sciences [q-bio]; Cancer; Life Sciences [q-bio]; Immunology

Andrey Pichugin, Olga V. Iarovaia, Alexey Gavrilov, Ilya Sklyar, Natalja Barinova, et al.. The IGH locus relocalizes to a "recombination compartment" in the perinucleolar region of differentiating B-lymphocytes. Oncotarget, 2017, 8 (25), pp.40079-40089. ⟨10.18632/oncotarget.16941⟩. ⟨hal-01560456⟩