| First Author | Hadebe S | Year | 2021 |
| Journal | J Allergy Clin Immunol | Volume | 148 |
| Issue | 1 | Pages | 99-109.e5 |
| PubMed ID | 33383090 | Mgi Jnum | J:312528 |
| Mgi Id | MGI:6764679 | Doi | 10.1016/j.jaci.2020.12.635 |
| Citation | Hadebe S, et al. (2021) Deletion of IL-4Ralpha signaling on B cells limits hyperresponsiveness depending on antigen load. J Allergy Clin Immunol 148(1):99-109.e5 |
| abstractText | BACKGROUND: B cells play an important role in allergies through secretion of IgE. IL-4 receptor alpha (IL-4Ralpha) 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-4Ralpha in B cells is not clearly defined. OBJECTIVE: We sought to find out whether IL-4Ralpha-responsive B cells or Be2 function was essential in experimental allergic asthma. METHODS: Mice lacking IL-4Ralpha on B cells (mb1(cre)IL-4Ralpha(-/lox)) or littermate controls (IL-4Ralpha(-/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 mug) or with low-dose house dust mite (<3 mug). We also adoptively transferred naive IL-4Ralpha(-/lox) or IL-4Ralpha(-/-) B cells into muMT(-/-) mice a day before sensitization or a day before challenge. We analyzed lung inflammation, cellular infiltrate, and airway hyperresponsiveness. RESULTS: We found that IL-4Ralpha signaling on B cells was important for optimal TH2 allergic immune responses mainly when the load of antigen is limited. IL-4Ralpha 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-4Ralpha 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. |
