Early Growth Response Genes 2 and 3 Regulate the Expression of Bcl6 and Differentiation of T Follicular Helper Cells

• Published in: The Journal of biological chemistry Vol. 290; no. 33; pp. 20455 - 20465
• Main Authors: Ogbe, Ane, Miao, Tizong, Symonds, Alistair L.J., Omodho, Becky, Singh, Randeep, Bhullar, Punamdip, Li, Suling, Wang, Ping
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.08.2015; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; antibody; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Cell Differentiation - physiology; cellular immune response; DNA-Binding Proteins - genetics; Early Growth Response Protein 2 - physiology; Early Growth Response Protein 3 - physiology; Gene Expression Regulation - physiology; Immunology; Mice; Mice, Inbred C57BL; Proto-Oncogene Proteins c-bcl-6; T helper cells; T-Lymphocytes, Helper-Inducer - chemistry; transcription factor; viral immunology; cellular immune response; T helper cells; transcription factor; antibody; viral immunology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M114.634816

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. Background: T follicular helper (Tfh) cells are essential for B cell responses against viruses and require B cell lymphoma 6 (BCL6). Results: Early growth response gene 2 (EGR2) and EGR3 intrinsically regulate Bcl6 and Tfh cells. Conclusion: EGR2 and -3 are novel regulators of BCL6-mediated Tfh development. Significance: In addition to controlling inflammation, EGR2 and -3 regulate Tfh function during antiviral immunoresponses.