Yin Yao1, Nan Wang1, Cai-Ling Chen1, Li Pan1, Zhi-Chao Wang1, Joseph Yunis2, Zhi-An Chen3, Yu Zhang4, Si-Tao Hu1, Xiao-Yan Xu5, Rong-Fei Zhu6, Di Yu3,4, Zheng Liu1. 1. Department of Otolaryngology-Head and Neck Surgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. 2. Faculty of Medicine, The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia. 3. Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia. 4. Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China. 5. Department of Otolaryngology-Head and Neck Surgery, China Resources & Wisco General Hospital, Wuhan, China. 6. Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract
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.
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 ARpatients 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 ARpatients. 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 ARpatients. Compared with those from healthy controls, Tfh2 cells from ARpatients 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 ARpatients. 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.
Authors: Fadwa A Abdelwahab; Khaled M Hassanein; Helal F Hetta; Mohamed O Abdelmalek; Asmaa M Zahran; Omnia El-Badawy Journal: Sci Rep Date: 2020-11-23 Impact factor: 4.379