title: Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers.
abstract: Follicular helper T (Tfh) cells access the B cell follicle to promote antibody responses and are particularly important for germinal center (GC) reactions. However, the molecular mechanisms of how Tfh cells are physically associated with GCs are incompletely understood. We report that the sphingosine-1-phosphate receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were ineffective in supporting GC responses compared with T cells deficient only in CXCR5. These results suggest that S1PR2 and CXCR5 cooperatively regulate localization of Tfh cells in GCs to support GC responses.
authors.affiliation: Laboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, JapanLaboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Saya
authors.initials: S
authors.lastname: Moriyama
authors.affiliation: Laboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Microbiology and Immunology and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Green
authors.affiliation: Laboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Hori
authors.affiliation: Laboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Noda, Chiba 278-0022, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Microbiology and Immunology and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Microbiology and Immunology and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
authors.affiliation: Laboratory for Tissue Dynamics, Laboratory for Lymphocyte Differentiation, Laboratory for Immune Homeostasis, and Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan PRESTO, Japan Science and Technology Agency, Saitama, Saitama 332-0012, Japan Graduate School of Medical Life Science, Yokohama City University, Yokohama 230-0045, Japan tokada@rcai.riken.jp.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Okada
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology*; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000276:immunology*; D000081025:Sphingosine-1-Phosphate Receptors; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: C513179:CXCR5 protein, mouse; D054380:Receptors, CXCR5; D049349:Receptors, Lysosphingolipid; D000081025:Sphingosine-1-Phosphate Receptors; C533955:sphingosine-1-phosphate receptor-2, mouse