IgD-activated mast cells induce IgE synthesis in B cells in nasal polyps - 17/09/18

Doi : 10.1016/j.jaci.2018.07.025

Guan-Ting Zhai, MD ^a, Hai Wang, MD ^a, Jing-Xian Li, MD ^a, Ping-Ping Cao, MD, PhD ^a, Wen-Xiu Jiang, MD ^a, Jia Song, MD ^a, Yin Yao, MD ^a, Zhi-Chao Wang, MD ^a, Zhe-Zheng Wang, MD ^a, Meng-Chen Wang, BS ^a, Bo Liao, MD, PhD ^a, Qi-Miao Feng, MD, PhD ^a, Xiang Lu, MD, PhD ^a, Heng Wang, MD, PhD ^a, Peisong Gao, MD, PhD ^b, Zheng Liu, MD, PhD ^a,^⁎
^a Department of Otolaryngology–Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
^b Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md

^∗Corresponding author: Zheng Liu, MD, PhD, Department of Otolaryngology–Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan 430030, China.Department of Otolaryngology–Head and Neck SurgeryTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyNo. 1095 Jiefang AveWuhan430030China

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Abstract

Background

Although upregulated expression of local IgD has been reported in patients with chronic rhinosinusitis (CRS), its function is unclear.

Objective

We sought to explore the expression and function of soluble IgD in patients with CRS, particularly CRS with nasal polyps.

Methods

IgD levels in sinonasal mucosa were analyzed by using RT-PCR and ELISA. Numbers and phenotypes of IgD⁺ cells were studied by means of immunohistochemistry, immunofluorescence, and flow cytometry. HMC-1 cells, a human mast cell line, and mast cells purified from eosinophilic polyps were cultured alone or with naive B cells purified from peripheral blood. The antigen specificity of nasal IgD was investigated by using ELISA.

Results

The mRNA expression of immunoglobulin heavy constant delta gene, numbers of IgD⁺ cells, and protein levels of secretory IgD in sinonasal mucosa were increased in patients with CRS with or without nasal polyps compared with control subjects. Numbers of IgD⁺ plasmablasts were increased in both eosinophilic and noneosinophilic polyps, whereas numbers of IgD⁺ mast cells were only increased in eosinophilic polyps. Cross-linking IgD induced serum preincubated HMC-1 cells and polyp mast cells to produce B-cell activating factor, IL-21, IL-4, and IL-13 and to promote IgM, IgG, IgA, and IgE production from B cells. In eosinophilic polyps expression of those B cell–stimulating factors in mast cells and close contact between mast cells and B cells were found. Moreover, positive correlations of total IgD levels with total IgE levels and eosinophilia and upregulation of specific IgD against house dust mites were discovered in eosinophilic polyps.

Conclusion

IgD-activated mast cells can facilitate IgE production and eosinophilic inflammation in patients with CRS with nasal polyps.

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Key words : B cell, chronic rhinosinusitis, eosinophil, IgD, IgE, mast cell, nasal polyps

Abbreviations used : BAFF, CRS, CRSsNP, CRSwNP, HRP, IGHD, NMC

Plan

	Supported by National Natural Science Foundation of China (NSFC) grants 81630024, 81570899, and 81325006 (to Z.L.), 81400449 (to P.-P.C.), 81700893 (to B.L.), and 81670911 (to X.L.) and a Hubei Province Natural Science Foundation grant 2017CFA016 (to Z.L.).
	Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.