title: V(D)J recombination process and the Pre-B to immature B-cells transition are altered in Fanca-/-mice.
abstract: B-lymphocytes in the bone marrow (BM) must generate a functional B-cell receptor and overcome the negative selection induced by reactivity with autoantigens. Two rounds of DNA recombination are required for the production of functional immunoglobulin heavy (Ig-HCs) and light (LCs) chains necessary for the continuation of B-lymphocyte development in the BM. Both rounds depend on the joint action of recombination activating gene-1 (RAG-1) and RAG-2 endonucleases with the DNA non-homologous end-joining pathway. Loss of the FANC gene leads to the chromosome breakage and cancer predisposition syndrome Fanconi anemia. Because the FANC proteins are involved in certain aspects of the recombination process, we sought to determine the impact of the FANC pathway on the Ig diversification process using Fanca-/-mice. In this work we demonstrated that Fanca-/-animals have a mild B-cell differentiation defect characterized by a specific alteration of the IgM-to IgM+transition of the B220lowB-cell population. Pre-B cells from Fanca-/-mice show evidence of impaired kLC rearrangement at the level of the Vk-Jk junction. Furthermore, Fanca-/-mice showed a skewed Vκ gene usage during formation of the LCs Vk-Jk junctions. Therefore, the Fanca protein appears as a yet unidentified factor involved in the primary diversification of Ig.
authors.affiliation: CNRS UMR 8200 - Gustave Roussy, Villejuif, France.|Université Paris Saclay, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, CNRS UMR8200, Villejuif, France.
authors.forename: Thuy Vy
authors.initials: TV
authors.lastname: Nguyen
authors.affiliation: CNRS UMR 8200 - Gustave Roussy, Villejuif, France.|Université Paris Saclay, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, CNRS UMR8200, Villejuif, France.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Pawlikowska
authors.affiliation: Université Paris Saclay, Orsay, France.|Université Paris Est, Créteil, Val de Marne, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Firlej
authors.affiliation: CNRS UMR 8200 - Gustave Roussy, Villejuif, France.|Université Paris Saclay, Orsay, France.|Equipe Labellisée Ligue Contre le Cancer, CNRS UMR8200, Villejuif, France.
authors.forename: Filippo
authors.initials: F
authors.lastname: Rosselli
authors.affiliation: CNRS UMR 8200 - Gustave Roussy, Villejuif, France.|Université Paris Saclay, Orsay, France.|Université Paris Descartes, Paris, France.
authors.forename: Saïd
authors.initials: S
authors.lastname: Aoufouchi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D059766:DNA End-Joining Repair / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D005199:Fanconi Anemia / Q000276:immunology; D052217:Fanconi Anemia Complementation Group A Protein / Q000276:immunology*; D051856:Fanconi Anemia Complementation Group Proteins / Q000276:immunology; D018398:Homeodomain Proteins / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000276:immunology; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D060152:V(D)J Recombination / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; C120277:Fanca protein, mouse; D052217:Fanconi Anemia Complementation Group A Protein; D051856:Fanconi Anemia Complementation Group Proteins; D018398:Homeodomain Proteins; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein