A Thpok-Directed Transcriptional Circuitry Promotes Bcl6 and Maf Expression to Orchestrate T Follicular Helper Differentiation
| Autor: | Golnaz Vahedi, Bao Tran, Marc K. Jenkins, Marion Pepper, Cameron McConkey, Yayi Gao, Mitchell T. McGinty, Rémy Bosselut, Masashi Watanabe, Mariah Balmaceno-Criss, Dorian B. McGavern, Yongmei Zhao, Qi Xiao, Melanie S. Vacchio, Allan Huang, Jyoti Shetty, Thomas Ciucci |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Transcription Genetic Cellular differentiation Immunology Major histocompatibility complex Lymphocyte Activation Article 03 medical and health sciences Mice 0302 clinical medicine hemic and lymphatic diseases medicine Immunology and Allergy Animals Transcription factor B cell B-Lymphocytes biology Germinal center Cell Differentiation Transcription Factor Maf T-Lymphocytes Helper-Inducer BCL6 Germinal Center Antibodies Neutralizing Cell biology Mice Inbred C57BL 030104 developmental biology Infectious Diseases medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Proto-Oncogene Proteins c-maf biology.protein Proto-Oncogene Proteins c-bcl-6 Female Antibody Transcription Factors |
| Zdroj: | Immunity |
| ISSN: | 1097-4180 |
| Popis: | Summary The generation of high-affinity neutralizing antibodies, the objective of most vaccine strategies, occurs in B cells within germinal centers (GCs) and requires rate-limiting “help” from follicular helper CD4+ T (Tfh) cells. Although Tfh differentiation is an attribute of MHC II-restricted CD4+ T cells, the transcription factors driving Tfh differentiation, notably Bcl6, are not restricted to CD4+ T cells. Here, we identified a requirement for the CD4+-specific transcription factor Thpok during Tfh cell differentiation, GC formation, and antibody maturation. Thpok promoted Bcl6 expression and bound to a Thpok-responsive region in the first intron of Bcl6. Thpok also promoted the expression of Bcl6-independent genes, including the transcription factor Maf, which cooperated with Bcl6 to mediate the effect of Thpok on Tfh cell differentiation. Our findings identify a transcriptional program that links the CD4+ lineage with Tfh differentiation, a limiting factor for efficient B cell responses, and suggest avenues to optimize vaccine generation. |
| Databáze: | OpenAIRE |
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