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.
CITATION STYLE
Weinstein, J. S., Herman, E. I., Lainez, B., Licona-Limón, P., Esplugues, E., Flavell, R., & Craft, J. (2016). T FH cells progressively differentiate to regulate the germinal center response. Nature Immunology, 17(10), 1197–1205. https://doi.org/10.1038/ni.3554
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