Production of antigen-specific IgE requires the properly timed help from TFH cells in a food allergy model

Abstract

Abstract Food allergy is characterized by food antigen (Ag)-specific IgE-mediated hypersensitivity. Follicular helper T cells (TFH) have been shown to control IgE production. However, the mechanisms for how TFH cells regulate IgE is not well understood. Utilizing a food allergy model in which mice are sensitized using peanut extract and cholera toxin through oral gavage, we found that peanut-specific IgE but not non-specific IgE requires two intragastric gavage (ig) Ag primings given 7 days apart. QPCR for germline expression of IgE showed that class-switching to IgE mainly occurs after second priming, which is different from IgG1. When NP-OVA and NP-KLH are used as Ags, we found that NP-specific IgE is still produced and thus maintaining the Ag specificity of TFH cells at both primings is not necessary. The expression of several IgE-promoting cytokines including IL-4 and IL-13 were upregulated in TFH cells upon the second priming. The requirement of IL-4 in antigen-specific IgE is validated using antibody blocking and Il4-heterzygote mice. Furthermore, we found that Ag-specific IgE is not produced when the timing between first and second timing is too short (2 days) or too long (2 weeks). TFH cells from these different timing showed different gene profile, indicating a possible role for the regulatory factors Fgl2 and CD39. These suppressive genes have not been associated with TFH function in food allergic IgE before. In conclusion, the production of Ag-specific IgE in gut priming requires a secondary priming and TFH cells play a crucial role through cytokines and other factors.