title: Bach2 regulates AID-mediated immunoglobulin gene conversion and somatic hypermutation in DT40 B cells.
abstract: The transcription factor Bach2 is required for germinal center formation, somatic hypermutation (SHM), and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process. We demonstrate that Bach2 promotes GCV by increasing the expression of AID. Importantly, we found that the regulation of AID is independent of Blimp-1 and that BACH2-deficient cells have altered expression of several genes regulating AID expression, stability and function. Furthermore, re-expression of BACH2 or AID in Bach2KO cells restored the SHM and GCV defects. These results demonstrate that Bach2 has a previously unappreciated role in the production of high-affinity antibodies.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.|Turku Doctoral Programme of Biomedical Sciences and Turku Doctoral Programme of Molecular Medicine, University of Turku, Turku, Finland.
authors.forename: Paulina M
authors.identifier: 0000-0002-2896-6806
authors.initials: PM
authors.lastname: Budzyńska
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Minna K
authors.initials: MK
authors.lastname: Kyläniemi
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Kallonen
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Anni I
authors.initials: AI
authors.lastname: Soikkeli
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Kalle-Pekka
authors.initials: KP
authors.lastname: Nera
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.|Departament of Medical Microbiology and Immunology, Turku University Hospital, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Lassila
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Alinikula
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002454:Cell Differentiation; D002645:Chickens; D003564:Cytidine Deaminase / Q000378:metabolism*; D005785:Gene Conversion; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D017578:Immunoglobulin Class Switching; D027041:Somatic Hypermutation, Immunoglobulin; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D014157:Transcription Factors; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AICDA; AID; Antibody diversification; B cells; Bach2; Ig somatic hypermutation; Immunoglobulin gene conversion; transcription factors