title: Essential Function for the Nuclear Protein Akirin2 in B Cell Activation and Humoral Immune Responses.
abstract: Akirin2, an evolutionarily conserved nuclear protein, is an important factor regulating inflammatory gene transcription in mammalian innate immune cells by bridging the NF-κB and SWI/SNF complexes. Although Akirin is critical for Drosophila immune responses, which totally rely on innate immunity, the mammalian NF-κB system is critical not only for the innate but also for the acquired immune system. Therefore, we investigated the role of mouse Akirin2 in acquired immune cells by ablating Akirin2 function in B lymphocytes. B cell-specific Akirin2-deficient (Cd19(Cre/+)Akirin2(fl/fl)) mice showed profound decrease in the splenic follicular (FO) and peritoneal B-1, but not splenic marginal zone (MZ), B cell numbers. However, both Akirin2-deficient FO and MZ B cells showed severe proliferation defect and are prone to undergo apoptosis in response to TLR ligands, CD40, and BCR stimulation. Furthermore, B cell cycling was defective in the absence of Akirin2 owing to impaired expression of genes encoding cyclin D and c-Myc. Additionally, Brg1 recruitment to the Myc and Ccnd2 promoter was severely impaired in Akirin2-deficient B cells. Cd19(Cre/+)Akirin2(fl/fl) mice showed impaired in vivo immune responses to T-dependent and -independent Ags. Collectively, these results demonstrate that Akirin2 is critical for the mitogen-induced B cell cycle progression and humoral immune responses by controlling the SWI/SNF complex, further emphasizing the significant function of Akirin2 not only in the innate, but also in adaptive immune cells.
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; Core Research for Engineering, Science, and Technology, Japan Science and Technology Agency, Kyoto 606-8507, Japan; and.
authors.forename: Sarang
authors.initials: S
authors.lastname: Tartey
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; Core Research for Engineering, Science, and Technology, Japan Science and Technology Agency, Kyoto 606-8507, Japan; and.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; Core Research for Engineering, Science, and Technology, Japan Science and Technology Agency, Kyoto 606-8507, Japan; and.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Wakabayashi
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; Core Research for Engineering, Science, and Technology, Japan Science and Technology Agency, Kyoto 606-8507, Japan; and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ori
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; Core Research for Engineering, Science, and Technology, Japan Science and Technology Agency, Kyoto 606-8507, Japan; and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mino
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; Core Research for Engineering, Science, and Technology, Japan Science and Technology Agency, Kyoto 606-8507, Japan; and otake@virus.kyoto-u.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D049109:Cell Proliferation; D056741:Cyclin D / Q000235:genetics / Q000276:immunology; D056742:Cyclin D2 / Q000235:genetics / Q000276:immunology; D004265:DNA Helicases / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D056724:Immunity, Humoral; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: C559423:Akirin2 protein, mouse; D018941:Antigens, CD19; D019013:CD40 Antigens; C486196:Ccnd2 protein, mouse; D056741:Cyclin D; D056742:Cyclin D2; C489428:Myc protein, mouse; D016328:NF-kappa B; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D051193:Toll-Like Receptors; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases