Follicular helper T cells are responsible for IgE responses to Der p 1 following house dust mite sensitization in mice. Issue 8 (6th June 2016)

• Record Type: Journal Article
• Authors: Noble, A.; Zhao, J.
• Is Part Of: Clinical & experimental allergy. Volume 46:Issue 8(2016:Aug.)
• Page Start: 1075
• Page End: 1082
• Publication Date: 2016-06-06
• Subjects: IgE -- follicular helper T cell -- Th2 cell -- Der p 1 -- house dust mite; Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12750
• Languages: English
• ISSNs: 0954-7894

Abstract

Summary: Background: 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. Objective: To determine whether Tfh cells are responsible for IgE responses to Der p 1 allergen after house dust mite (HDM)‐induced allergic sensitization. Methods: Mice deficient in Tfh cells were sensitized to HDM and Der p 1‐specific IgE measured by ELISA. Results: 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. Conclusions and Clinical Relevance: 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.