title: Th17 effector cells support B cell responses outside of germinal centres.
abstract: Th17 cells are pro-inflammatory CD4⁺T cells, which are important in immune responses against fungal pathogens and extracellular bacteria and have also been implicated in various autoimmune syndromes. However, their role in supporting B cell responses in these scenarios remains unclear, representing a significant lapse in our understanding of the role Th17 play in vaccine responses and the regulation of autoimmunity. We employed T cell and B cell receptor transgenic mice specific for model antigens, and adoptive transfer approaches that allowed the tracking of cognate B and T cells in situ and ex vivo using immunological methods. We have found that T cells activated under Th17 polarising conditions have a greater capacity to provide cognate B cell help compared with Th1 polarised populations, supporting higher expansion of antigen specific B cells and enhanced antibody titres. This advantage is associated with the increased persistence of Th17 polarised cells in areas of the lymph nodes where they can provide help (i.e. the B cell follicles). Also the Th17 cells are characterised by their higher expression of ICOS, a costimulatory molecule important for B cell help. Surprisingly, contrary to published reports, Th17 cells were not detected inside germinal centres, although they were found in close proximity to cognate B cells in the follicle early in the genesis of the humoral immune response. These data indicate that, Th17 cells have a more significant role earlier in the initiation/development of the germinal centre response and/or germinal centre-independent events, consistent with their early effector status.
authors.affiliation: Institute of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom. Agapitos.Patakas@glasgow.ac.uk
authors.forename: Agapitos
authors.initials: A
authors.lastname: Patakas
authors.forename: Robert A
authors.initials: RA
authors.lastname: Benson
authors.forename: David R
authors.initials: DR
authors.lastname: Withers
authors.forename: Paola
authors.initials: P
authors.lastname: Conigliaro
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: James M
authors.initials: JM
authors.lastname: Brewer
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D060889:Inducible T-Cell Co-Stimulator Protein