title: TFH cells progressively differentiate to regulate the germinal center response.
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.
authors: Department of Internal Medicine (Rheumatology) Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Jason S
authors: JS
authors: Weinstein
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Edward I
authors: EI
authors: Herman
authors: Department of Internal Medicine (Rheumatology) Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Begoña
authors: B
authors: Lainez
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Paula
authors: P
authors: Licona-Limón
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Enric
authors: E
authors: Esplugues
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.|Howard Hughes Medical Institute.
authors: Richard
authors: R
authors: Flavell
authors: Department of Internal Medicine (Rheumatology) Yale University School of Medicine, New Haven, CT 06520, USA.|Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Joe
authors: J
authors: Craft
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D009559:Nippostrongylus / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017206:Strongylida Infections; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D015704:CD4 Antigens; D007378:Interleukins; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D015847:Interleukin-4; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000098546:Interleukin-21