Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4‐Related Disease. Issue 11 (29th August 2018)

• Record Type: Journal Article
• Authors: Chen, Yu; Lin, Wei; Yang, Hongxian; Wang, Mu; Zhang, Panpan; Feng, Ruie; Chen, Hua; Peng, Linyi; Zhang, Xuan; Zhao, Yan; Zeng, Xiaofeng; Zhang, Fengchun; Zhang, Wen; Lipsky, Peter E.
• Is Part Of: Arthritis & rheumatology. Volume 70:Issue 11(2018)
• Page Start: 1853
• Page End: 1865
• Publication Date: 2018-08-29
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.40556
• Languages: English
• ISSNs: 2326-5191

Abstract

Abstract : Objective: To determine the number and function of follicular helper T (Tfh) cell subsets in IgG4‐related disease (IgG4‐RD). Methods: Mononuclear cells from the peripheral blood and involved tissue of patients with IgG4‐RD were assessed for Tfh cells and their subsets, and levels of B cell lymphoma 6 (Bcl‐6), B lymphocyte–induced maturation protein 1 (BLIMP‐1), and interleukin‐21 (IL‐21) messenger RNA (mRNA). Immunohistochemical and immunofluorescence techniques were used to assess the involved tissue of patients to determine the location of IL‐21, Bcl‐6, and CD4+CXCR5+ Tfh cells. Furthermore, the ability of circulating Tfh (cTfh) cell subsets to induce B cell proliferation, apoptosis, and differentiation and to produce IgG4 was explored in cell cocultures in vitro. Results: Frequencies of cTfh cells were significantly increased in the peripheral blood of patients with IgG4‐RD, and even higher frequencies were observed in the involved tissue. Percentages of programmed cell death protein 1 in CD4+CXCR5+ICOS+ cTfh cells were positively correlated with the serum levels of IgG and IgG4, IgG4:IgG ratio, number of involved organs, and frequency of CD19+CD24−CD38 high plasmablasts/plasma cells. Levels of BLIMP‐1 and IL‐21 mRNA in peripheral CD4+ T cells were increased in patients with IgG4‐RD compared to healthy controls, and this was correlated with the levels of serum IgG4. Moreover, in the involved tissue, Bcl‐6, IL‐21, and Tfh cells were highly expressed. Compared to cTfh cells from healthy controls, cTfh cells from patients with IgG4‐RD could facilitate B cell proliferation and inhibit B cell apoptosis more efficiently, and enhanced the differentiation of naive B cells into switched memory B cells and plasmablasts/plasma cells, with a resultant increase in the secretion of IgG4. Notably, the cTfh1 and cTfh2 cell subsets were the most effective at providing B cell help. Conclusion: Tfh cell subsets are expanded in IgG4‐RD and may play pivotal roles in the pathogenesis of the disease.