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Yao, Yin; Wang, Nan; Chen, Cai‐Ling; Pan, Li; Wang, Zhi‐Chao; Yunis, Joseph; Chen, Zhi‐An; Zhang, Yu; Hu, Si‐Tao; Xu, Xiao‐Yan; Zhu, Rong‐Fei; Yu, Di; Liu, Zheng
Allergy (Copenhagen), October 2020, 2020-10-00, 20201001, Volume: 75, Issue: 10Journal Article
Background The contribution of B‐cell subsets and T‐B cell interaction to the pathogenesis of allergic rhinitis (AR) and mechanisms of allergen immunotherapy (AIT) remain poorly understood. This study aimed to outline circulating B‐cell signature, the underlying mechanism, and its association with clinical response to AIT in patients with AR. Methods IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies and phenotypes of B cells. Correlations between B cells, T cells, antigen‐specific IgE, and disease severity in AR patients were investigated. Switched memory B cells were co‐cultured with type 2 follicular helper T (Tfh2) cells and follicular regulatory T (Tfr) cells. Associations between B‐cell subsets and clinical benefits of AIT were analyzed. Results Frequencies and absolute numbers of circulating memory B cells were increased in AR patients. CD23 expression on CD19+CD20+CD27+IgD− switched memory B cells was significantly enhanced and positively correlated with antigen‐specific IgE levels, symptom scores, and Tfh2/Tfr cell ratio in AR patients. Compared with those from healthy controls, Tfh2 cells from AR patients had a greater capacity to induce CD23 expression on switched memory B cells via IL‐4, which was unable to be sufficiently suppressed by AR‐associated Tfr cells with defective IL‐10 expression. CD23 expression on switched memory B cells was downregulated after 12‐month AIT, which positively associated with disease remission in AR patients. Conclusion T‐B cell interaction, bridged by CD23 expression particularly on switched memory B cells, may be involved in the disease pathogenesis and mechanism of AIT in patients with AR. Circulating memory B cells are increased in AR patients. The enhanced expression of CD23 on switched memory B cells correlates with antigen‐specific IgE levels, symptom scores, and allergen immunotherapy efficacy in AR patients. Tfh2 cells from AR patients have a greater capacity to induce CD23 expression on switched memory B cells via IL‐4, which is unable to be sufficiently suppressed by AR‐associated Tfr cells with defective IL‐10 expression. Abbreviations: AIT, allergen immunotherapy; AR, allergic rhinitis; HC, healthy controls; NSM, nonswitched memory; SM, switched memory; Tfh2, type 2 follicular helper T cells; Tfr, follicular regulatory T cell.
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