title: Phenotypic Tfh development promoted by CXCR5-controlled re-localization and IL-6 from radiation-resistant cells.
abstract: How follicular T-helper (Tfh) cells develop is incompletely understood. We find that, upon antigen exposure in vivo, both naïve and antigen-experienced T cells sequentially upregulate CXCR5 and Bcl6 within the first 24 h, relocate to the T-B border, and give rise to phenotypic Bcl6(+)CXCR5(+) Tfh cells before the first cell division. CXCR5 upregulation is more dependent on ICOS costimulation than that of Bcl6, and early Bcl6 induction requires T-cell expression of CXCR5 and, presumably, relocation toward the follicle. This early and rapid upregulation of CXCR5 and Bcl6 depends on IL-6 produced by radiation-resistant cells. These results suggest that a Bcl6(hi)CXCR5(hi) phenotype does not automatically define a Tfh lineage but might reflect a state of antigen exposure and non-commitment to terminal effector fates and that niches in the T-B border and/or the follicle are important for optimal Bcl6 induction and maintenance.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China. xin.chen01@foxmail.com.|Laboratory of Dynamic Immunobiology, Institute for Immunology, School of Medicine, Tsinghua University, Beijing, 100084, China. xin.chen01@foxmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.|Laboratory of Dynamic Immunobiology, Institute for Immunology, School of Medicine, Tsinghua University, Beijing, 100084, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Tingxin
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.|Laboratory of Dynamic Immunobiology, Institute for Immunology, School of Medicine, Tsinghua University, Beijing, 100084, China.
authors.forename: Longyan
authors.initials: L
authors.lastname: Wu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China. qihai@tsinghua.edu.cn.|Laboratory of Dynamic Immunobiology, Institute for Immunology, School of Medicine, Tsinghua University, Beijing, 100084, China. qihai@tsinghua.edu.cn.
authors.forename: Hai
authors.initials: H
authors.lastname: Qi
mesh_terms: D000818:Animals; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5 / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
chemical_list: C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D015850:Interleukin-6; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D023201:CD40 Ligand
keywords: Bcl6; CXCR5; IL-6; Tfh; radiation-resistant cell