title: Early Growth Response Genes 2 and 3 Regulate the Expression of Bcl6 and Differentiation of T Follicular Helper Cells.
abstract: T follicular helper (Tfh) cells support differentiation of B cells to plasma cells and high affinity antibody production in germinal centers (GCs), and Tfh differentiation requires the function of B cell lymphoma 6 (BCL6). We have now discovered that early growth response gene 2 (EGR2) and EGR3 directly regulate the expression of Bcl6 in Tfh cells, which is required for their function in regulation of GC formation. In the absence of EGR2 and -3, the expression of BCL6 in Tfh cells is defective, leading to impaired differentiation of Tfh cells, resulting in a failure to form GCs following virus infection and defects in production of antiviral antibodies. Enforced expression of BCL6 in EGR2/3-deficient CD4 T cells partially restored Tfh differentiation and GC formation in response to virus infection. Our findings demonstrate a novel function of EGR2/3 that is important for Tfh cell development and Tfh cell-mediated B cell immune responses.
authors.affiliation: From the Division of Biosciences, Department of Life Sciences, Brunel University, Kingston Lane, UB8 3PH, United Kingdom and the Blizard Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AD, United Kingdom.
authors.forename: Ane
authors.initials: A
authors.lastname: Ogbe
authors.affiliation: the Blizard Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AD, United Kingdom.
authors.forename: Tizong
authors.initials: T
authors.lastname: Miao
authors.affiliation: the Blizard Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AD, United Kingdom.
authors.forename: Alistair L J
authors.initials: AL
authors.lastname: Symonds
authors.affiliation: From the Division of Biosciences, Department of Life Sciences, Brunel University, Kingston Lane, UB8 3PH, United Kingdom and.
authors.forename: Becky
authors.initials: B
authors.lastname: Omodho
authors.affiliation: From the Division of Biosciences, Department of Life Sciences, Brunel University, Kingston Lane, UB8 3PH, United Kingdom and.
authors.forename: Randeep
authors.initials: R
authors.lastname: Singh
authors.affiliation: From the Division of Biosciences, Department of Life Sciences, Brunel University, Kingston Lane, UB8 3PH, United Kingdom and.
authors.forename: Punamdip
authors.initials: P
authors.lastname: Bhullar
authors.affiliation: From the Division of Biosciences, Department of Life Sciences, Brunel University, Kingston Lane, UB8 3PH, United Kingdom and su-ling.li@brunel.ac.uk.
authors.forename: Suling
authors.initials: S
authors.lastname: Li
authors.affiliation: the Blizard Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AD, United Kingdom p.wang@qmul.ac.uk.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D051767:Early Growth Response Protein 2 / Q000502:physiology*; D051776:Early Growth Response Protein 3 / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051560:Proto-Oncogene Proteins c-bcl-6; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry*
chemical_list: C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C497369:Egr3 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D051776:Early Growth Response Protein 3
keywords: T helper cells; antibody; cellular immune response; transcription factor; viral immunology