Deletion of IL-4Rα signaling on B cells limits hyperresponsiveness depending on antigen load
Sabelo Hadebe1, Jermaine Khumalo2, Sandisiwe Mangali2
1Division of Immunology, and South African Medical Research Council Immunology of Infectious Diseases, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
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 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 sensitized and challenged with high-dose house dust mite (>10 μg) or with low-dose house dust mite (<3 μg). We also adoptively transferred naive IL-4Rα-/lox or IL-4Rα-/- B cells into μMT-/- mice a day before sensitization or a day before challenge. We analyzed lung inflammation, cellular infiltrate, and airway hyperresponsiveness.
Results:
We found that IL-4Rα signaling on B cells was important for optimal TH2 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:
IL-4Rα signaling on B cells is deleterious in allergic asthma because it is required for optimal TH2 responses, Be2 function, germinal center formation, and T follicular helper cells, especially when the load of the antigen is limiting.
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