title: Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype.
abstract: T follicular helper (Tfh) cells provide help to B cells and are crucial for establishment of germinal center (GC) reactions, including production of high-affinity antibodies and generation of memory B cells and long-lived plasma cells. Here we report that the magnitude of the Tfh cell response was dictated by the amount of antigen and directly correlated with the magnitude of the GC B cell response. In addition, maintenance of the Tfh cell phenotype required sustained antigenic stimulation by GC B cells. In lymphopenic conditions, a strong and prolonged Tfh cell response led to bystander B cell activation, hypergammaglobulinemia, and production of poly- and self-reactive antibodies. These data demonstrate that antigen dose determines the size and duration of the Tfh cell response and GC reaction, highlight the transient nature of the Tfh cell phenotype, and suggest a link between overstimulation of Tfh cells and the development of dysregulated humoral immune responses.
authors.affiliation: Institute for Research in Biomedicine, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. dirk.baumjohann@ucsf.edu
authors.forename: Dirk
authors.initials: D
authors.lastname: Baumjohann
authors.forename: Silvia
authors.initials: S
authors.lastname: Preite
authors.forename: Andrea
authors.initials: A
authors.lastname: Reboldi
authors.forename: Francesca
authors.initials: F
authors.lastname: Ronchi
authors.forename: K Mark
authors.initials: KM
authors.lastname: Ansel
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007114:Immunization / Q000379:methods; D016130:Immunophenotyping; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000276:immunology / Q000378:metabolism; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D000941:Antigens; D017252:CD3 Complex; D019013:CD40 Antigens; C513179:CXCR5 protein, mouse; C485468:Cd3e protein, mouse; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008164:Luminescent Proteins; D054380:Receptors, CXCR5; D023201:CD40 Ligand; D010047:Ovalbumin