Deletion of IL-4Rα signaling on B cells limits hyperresponsiveness depending on antigen load
Sabelo Hadebe, Jermaine Khumalo, Sandisiwe Mangali, Nontobeko Mthembu, Hlumani Ndlovu, Martyna Scibiorek, Amkele Ngomti, Frank Kirstein, Frank Brombacher
Abstract
BACKGROUND: B cells play an important role in allergies through secretion of IgE. IL-4 receptor α (IL-4Rα) is key in allergic asthma and regulates type 2 cytokine production, IgE secretion, and airway hyperresponsiveness. 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 signaling via IL-4Rα in B cells is not clearly defined. OBJECTIVE: We sought to find out whether IL-4Rα-responsive B cells or Be2 function was essential in experimental allergic asthma. METHODS: mice a day before sensitization or a day before challenge. We analyzed lung inflammation, cellular infiltrate, and airway hyperresponsiveness. RESULTS: 2 allergic immune responses mainly when the load of antigen is limited. IL-4Rα signaling on B cells was essential for germinal centers and in the effector phase of allergic responses. Be2 cells were essential in airway hyperresponsiveness, but not in other parameters. CONCLUSIONS: 2 responses, Be2 function, germinal center formation, and T follicular helper cells, especially when the load of the antigen is limiting.