1. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.
- Author
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Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, Dent AL, Craft J, and Crotty S
- Subjects
- Animals, Antibody Formation, Arenaviridae Infections immunology, B-Lymphocytes immunology, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes immunology, Cell Differentiation, Cell Lineage, Cytokines metabolism, DNA-Binding Proteins genetics, Gene Expression Regulation, Germinal Center cytology, Germinal Center immunology, Lymphocyte Activation, Lymphocytic choriomeningitis virus immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Positive Regulatory Domain I-Binding Factor 1, Proto-Oncogene Proteins c-bcl-6, RNA, Messenger genetics, RNA, Messenger metabolism, Signal Transduction, T-Lymphocyte Subsets cytology, T-Lymphocytes, Helper-Inducer cytology, Transcription Factors genetics, DNA-Binding Proteins metabolism, T-Lymphocyte Subsets immunology, T-Lymphocytes, Helper-Inducer immunology, Transcription Factors metabolism
- Abstract
Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits T(FH) differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that T(FH) cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in T(FH) differentiation.
- Published
- 2009
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