Deletion of IL-4R$α$ signalling on B cells limits hyperresponsiveness depending on antigen-load. Hadebe, S., Khumalo, J., Mangali, S., Mthembu, N., Ndlovu, H., Scibiorek, M., Ngomti, A., Kirstein, F., & Brombacher, F. Journal of Allergy and Clinical Immunology, 148(1):99–109.E5, J Allergy Clin Immunol, dec, 2021. ![Deletion of IL-4R$α$ signalling on B cells limits hyperresponsiveness depending on antigen-load. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Background: B cells play an important role in allergies through secretion of IgE. Interleukin 4 receptor $α$ (IL-4R$α$) 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-4R$α$ in B cells is not clearly defined. Objective: Here, we asked whether IL-4R$α$-responsive B cells or Be2 function were essential in experimental allergic asthma. Methods: Mice lacking IL-4R$α$ on B cells (mb1creIL-4R$α$-/lox) or littermate controls (IL-4R$α$-/lox) and mice lacking IL-4 or IL-4/IL-13 on B cells were sensitised and challenged with high dose HDM (\textgreater10$μ$g) or with low dose HDM (\textless3 $μ$g). We also adoptively transferred naïve IL-4R$α$-/lox or IL-4R$α$-/- B cells into $μ$MT-/- mice a day before sensitisation or a day before challenge. We analysed lung inflammation, cellular infiltrate and AHR. Results: We found that IL-4R$α$ signalling on B cells was important for optimal TH2 allergic immune responses mainly when the load of antigen is limited. IL-4R$α$ 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-4R$α$ 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.
@article{Hadebe2020,
abstract = {Background: B cells play an important role in allergies through secretion of IgE. Interleukin 4 receptor $\alpha$ (IL-4R$\alpha$) 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-4R$\alpha$ in B cells is not clearly defined. Objective: Here, we asked whether IL-4R$\alpha$-responsive B cells or Be2 function were essential in experimental allergic asthma. Methods: Mice lacking IL-4R$\alpha$ on B cells (mb1creIL-4R$\alpha$-/lox) or littermate controls (IL-4R$\alpha$-/lox) and mice lacking IL-4 or IL-4/IL-13 on B cells were sensitised and challenged with high dose HDM ({\textgreater}10$\mu$g) or with low dose HDM ({\textless}3 $\mu$g). We also adoptively transferred na{\"{i}}ve IL-4R$\alpha$-/lox or IL-4R$\alpha$-/- B cells into $\mu$MT-/- mice a day before sensitisation or a day before challenge. We analysed lung inflammation, cellular infiltrate and AHR. Results: We found that IL-4R$\alpha$ signalling on B cells was important for optimal TH2 allergic immune responses mainly when the load of antigen is limited. IL-4R$\alpha$ 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-4R$\alpha$ 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.},
author = {Hadebe, Sabelo and Khumalo, Jermaine and Mangali, Sandisiwe and Mthembu, Nontobeko and Ndlovu, Hlumani and Scibiorek, Martyna and Ngomti, Amkele and Kirstein, Frank and Brombacher, Frank},
doi = {10.1016/j.jaci.2020.12.635},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hadebe et al. - 2021 - Deletion of IL-4R$\alpha$ signalling on B cells limits hyperresponsiveness depending on antigen-load.pdf:pdf},
issn = {00916749},
journal = {Journal of Allergy and Clinical Immunology},
keywords = {Frank Brombacher,Jermaine Khumalo,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,OA,PubMed Abstract,Sabelo Hadebe,doi:10.1016/j.jaci.2020.12.635,fund{\_}ack,original,pmid:33383090},
mendeley-tags = {OA,fund{\_}ack,original},
month = {dec},
number = {1},
pages = {99--109.E5},
pmid = {33383090},
publisher = {J Allergy Clin Immunol},
title = {{Deletion of IL-4R$\alpha$ signalling on B cells limits hyperresponsiveness depending on antigen-load.}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0091674920324258},
volume = {148},
year = {2021}
}
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Methods: Mice lacking IL-4R$α$ on B cells (mb1creIL-4R$α$-/lox) or littermate controls (IL-4R$α$-/lox) and mice lacking IL-4 or IL-4/IL-13 on B cells were sensitised and challenged with high dose HDM (\\textgreater10$μ$g) or with low dose HDM (\\textless3 $μ$g). We also adoptively transferred naïve IL-4R$α$-/lox or IL-4R$α$-/- B cells into $μ$MT-/- mice a day before sensitisation or a day before challenge. We analysed lung inflammation, cellular infiltrate and AHR. Results: We found that IL-4R$α$ signalling on B cells was important for optimal TH2 allergic immune responses mainly when the load of antigen is limited. IL-4R$α$ 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-4R$α$ 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.","author":[{"propositions":[],"lastnames":["Hadebe"],"firstnames":["Sabelo"],"suffixes":[]},{"propositions":[],"lastnames":["Khumalo"],"firstnames":["Jermaine"],"suffixes":[]},{"propositions":[],"lastnames":["Mangali"],"firstnames":["Sandisiwe"],"suffixes":[]},{"propositions":[],"lastnames":["Mthembu"],"firstnames":["Nontobeko"],"suffixes":[]},{"propositions":[],"lastnames":["Ndlovu"],"firstnames":["Hlumani"],"suffixes":[]},{"propositions":[],"lastnames":["Scibiorek"],"firstnames":["Martyna"],"suffixes":[]},{"propositions":[],"lastnames":["Ngomti"],"firstnames":["Amkele"],"suffixes":[]},{"propositions":[],"lastnames":["Kirstein"],"firstnames":["Frank"],"suffixes":[]},{"propositions":[],"lastnames":["Brombacher"],"firstnames":["Frank"],"suffixes":[]}],"doi":"10.1016/j.jaci.2020.12.635","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Hadebe et al. - 2021 - Deletion of IL-4R$α$ signalling on B cells limits hyperresponsiveness depending on antigen-load.pdf:pdf","issn":"00916749","journal":"Journal of Allergy and Clinical Immunology","keywords":"Frank Brombacher,Jermaine Khumalo,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,OA,PubMed Abstract,Sabelo Hadebe,doi:10.1016/j.jaci.2020.12.635,fund_ack,original,pmid:33383090","mendeley-tags":"OA,fund_ack,original","month":"dec","number":"1","pages":"99–109.E5","pmid":"33383090","publisher":"J Allergy Clin Immunol","title":"Deletion of IL-4R$α$ signalling on B cells limits hyperresponsiveness depending on antigen-load.","url":"https://linkinghub.elsevier.com/retrieve/pii/S0091674920324258","volume":"148","year":"2021","bibtex":"@article{Hadebe2020,\r\nabstract = {Background: B cells play an important role in allergies through secretion of IgE. 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