Deletion of IL-4Rα Signaling on B Cells Limits Hyperresponsiveness Depending on Antigen Load

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2020 Dec 31

PMID 33383090

Citations 7

Authors

Sabelo Hadebe

Jermaine Khumalo

Sandisiwe Mangali

Nontobeko Mthembu

Hlumani Ndlovu

Martyna Scibiorek

Amkele Ngomti

Frank Kirstein

Frank Brombacher

Affiliations

Soon will be listed here.

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 lacking IL-4Rα on B cells (mb1IL-4Rα) or littermate controls (IL-4Rα) 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 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 T2 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 T2 responses, Be2 function, germinal center formation, and T follicular helper cells, especially when the load of the antigen is limiting.

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