1. TFH cells progressively differentiate to regulate the germinal center response.
- Author
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Weinstein JS, Herman EI, Lainez B, Licona-Limón P, Esplugues E, Flavell R, and Craft J
- Subjects
- Animals, Antibody Affinity, CD4 Antigens metabolism, Cell Communication, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Humans, Interleukin-4 metabolism, Interleukins genetics, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mutation genetics, Positive Regulatory Domain I-Binding Factor 1, Strongylida Infections, Transcription Factors genetics, Transcription Factors metabolism, B-Lymphocytes immunology, Germinal Center immunology, Interleukins metabolism, Nippostrongylus immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Germinal center (GC) B cells undergo affinity selection, which depends on interactions with CD4(+) follicular helper T cells (TFH cells). We found that TFH cells progressed through transcriptionally and functionally distinct stages and provided differential signals for GC regulation. They initially localized proximally to mutating B cells, secreted interleukin 21 (IL-21), induced expression of the transcription factor Bcl-6 and selected high-affinity B cell clones. As the GC response evolved, TFH cells extinguished IL-21 production and switched to IL-4 production, showed robust expression of the co-stimulatory molecule CD40L, and promoted the development of antibody-secreting B cells via upregulation of the transcription factor Blimp-1. Thus, TFH cells in the B cell follicle progressively differentiate through stages of localization, cytokine production and surface ligand expression to 'fine tune' the GC reaction.
- Published
- 2016
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