Immunoglobulin D-Activated Mast Cells Induce IgE Synthesis in B Cells in Nasal Polyps

Publication date: Available online 10 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Guan-Ting Zhai, Hai Wang, Jing-Xian Li, Ping-Ping Cao, Wen-Xiu Jiang, Jia Song, Yin Yao, Zhi-Chao Wang, Zhe-Zheng Wang, Meng-Chen Wang, Bo Liao, Qi-Miao Feng, Xiang Lu, Heng Wang, Peisong Gao, Zheng Liu

Abstract

Background

Although up-regulated expression of local IgD has been reported in chronic rhinosinusitis (CRS), its function is unclear.

Objective

To explore the expression and function of soluble IgD in CRS, particularly CRS with nasal polyps (CRSwNP).

Methods

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

Results

The mRNA expression of immunoglobulin heavy constant delta gene, the numbers of IgD⁺ cells, and the protein levels of secretory IgD in sinonasal mucosa were increased in CRS patients with or without nasal polyps compared to controls. The numbers of IgD⁺ plasmablasts were increased in both eosinophilic and non-eosinophilic polyps, whereas the numbers of IgD⁺ mast cells were only increased in eosinophilic polyps. Crosslinking IgD induced serum pre-incubated 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, the expression of those B cell-stimulating factors in mast cells and close contacts between mast cells and B cells were found. Moreover, positive correlations of total IgD with total IgE and eosinophilia, and up-regulation of specific IgD against house dust mites were discovered in eosinophilic polyps.

Conclusion

IgD-activated mast cells may facilitate IgE production and eosinophilic inflammation in CRSwNP.

https://ift.tt/2M9z1Dc