Deletion of IL-4Rα signalling on B cells limits hyperresponsiveness depending on antigen-load.

Background B cells play an important role in allergies through secretion of IgE. Interleukin 4 receptor α (IL-4Rα) is key in allergic asthma and regulates type 2 cytokine production, IgE secretion and airway hyperresponsiveness (AHR). IL-4 activation of B cells is essential for class-switching and contributes to the induction of B effector 2 (Be2) cells. The role of Be2 cells and signalling via IL-4Rα in B cells is not clearly defined. Objective Here, we asked whether IL-4Rα-responsive B cells or Be2 function were essential in experimental allergic asthma. Methods Mice lacking IL-4Rα on B cells (mb1creIL-4Rα-/lox) or littermate controls (IL-4Rα-/lox) and mice lacking IL-4 or IL-4/IL-13 on B cells were sensitised and challenged with high dose HDM (>10μg) or with low dose HDM ( Results We found that IL-4Rα signalling on B cells was important for optimal TH2 allergic immune responses mainly when the load of antigen is limited. IL-4Rα signalling on B cells was essential for germinal centres (GC) and in the effector phase of allergic responses. Be2 cells were essential in AHR, but not in in other parameters. Conclusion IL-4Rα signalling on B cells is deleterious in allergic asthma as it is required for optimal TH2 responses, Be2 function, GC formation and T follicular helper cells, especially when the load of the antigen is limiting.