Early Growth Response Genes 2 and 3 Regulate the Expression of Bcl6 and Differentiation of T Follicular Helper Cells |
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| Authors: | Ane Ogbe Tizong Miao Alistair L J Symonds Becky Omodho Randeep Singh Punamdip Bhullar Suling Li Ping Wang |
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| Institution: | 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 |
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| 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. |
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