title: T follicular helper cells have distinct modes of migration and molecular signatures in naive and memory immune responses.
abstract: B helper follicular T (Tfh) cells are critical for long-term humoral immunity. However, it remains unclear how these cells are recruited and contribute to secondary immune responses. Here we show that primary Tfh cells segregate into follicular mantle (FM) and germinal center (GC) subpopulations that display distinct gene expression signatures. Restriction of the primary Tfh cell subpopulation in the GC was mediated by downregulation of chemotactic receptor EBI2. Following collapse of the GC, memory T cells persisted in the outer follicle where they scanned CD169(+) subcapsular sinus macrophages. Reactivation and intrafollicular expansion of these follicular memory T cells in the subcapsular region was followed by their extrafollicular dissemination via the lymphatic flow. These data suggest that Tfh cells integrate their antigen-experience history to focus T cell help within the GC during primary responses but act rapidly to provide systemic T cell help after re-exposure to the antigen.
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Dan
authors.initials: D
authors.lastname: Suan
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Akira
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Imogen
authors.initials: I
authors.lastname: Moran
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Bourne
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Jana R
authors.initials: JR
authors.lastname: Hermes
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Centre for Applied Medical Research, 405 Liverpool Street, Darlinghurst, NSW 2010 Australia.
authors.forename: Mehreen
authors.initials: M
authors.lastname: Arshi
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Hampton
authors.affiliation: Kyoto University Graduate School of Medicine, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Tomura
authors.affiliation: University of Tsukuba, Ibaraki Prefecture, Tsukuba 305-8572, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miwa
authors.affiliation: St Vincent's Centre for Applied Medical Research, 405 Liverpool Street, Darlinghurst, NSW 2010 Australia.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Warren
authors.initials: W
authors.lastname: Kaplan
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Elissa K
authors.initials: EK
authors.lastname: Deenick
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Brink
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia. Electronic address: t.chtanova@garvan.org.au.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Chtanova
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia. Electronic address: t.phan@garvan.org.au.
authors.forename: Tri Giang
authors.initials: TG
authors.lastname: Phan
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D056724:Immunity, Humoral; D007156:Immunologic Memory; D051379:Mice; D018345:Mice, Knockout; D061251:Primary Cell Culture; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology
chemical_list: C543809:Gpr183 protein, mouse; D043562:Receptors, G-Protein-Coupled; D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse