title: Follicular helper T cells are responsible for IgE responses to Der p 1 following house dust mite sensitization in mice.
abstract: Th2 cells have long been considered responsible for the switching of B cells to production of IgE during cognate interaction, primarily due to their expression of CD40L and secretion of IL-4. This concept has been challenged by the more recent definition of follicular helper T cells (Tfh) as the key T cell subset in B cell isotype switching, due to their physical location at the boundary of T cell:B cell areas in lymphoid follicles and ability to express IL-4 and CD40L.
  
  
  
  To determine whether Tfh cells are responsible for IgE responses to Der p 1 allergen after house dust mite (HDM)-induced allergic sensitization.
  
  
  
  Mice deficient in Tfh cells were sensitized to HDM and Der p 1-specific IgE measured by ELISA.
  
  
  
  Mice with a mutation in T cell-expressed IL-6R were unable to expand Tfh populations after HDM sensitization, and their anti-Der p 1 IgE, IgG1 and total IgE responses were reduced by 80-90% compared with wild-type mice. These animals displayed unaltered lung Th2 and eosinophilic responses after intranasal HDM challenge and normal IL-4 production, but B cell infiltration of the airways was abrogated.
  
  
  
  Our data indicate that Tfh cells are largely responsible for switching B cells to IgE synthesis, most likely via an IgG1(+) intermediate. However, Th2 cells are the major source of IL-4 during HDM sensitization and this might contribute to IgE synthesis at a stage distal to Tfh-mediated isotype switching. The IL-6/follicular helper T cell pathway is a potential therapeutic target in allergic disease.
authors.affiliation: MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Noble
authors.affiliation: MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1
keywords: Der p 1; IgE; Th2 cell; follicular helper T cell; house dust mite