Arthritis research & therapy · 2014
B cell subsets and dysfunction of regulatory B cells in IgG4-related diseases and primary Sjögren's syndrome: the similarities and differences.
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Lin Wei, Jin Lixia, Chen Hua, Wu Qingjun, Fei Yunyun, Zheng Wenjie, Wang Qian, Li Ping, Li Yongzhe, Zhang Wen, Zhao Yan, Zeng Xiaofeng, Zhang Fengchun
Аннотация
INTRODUCTION: IgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune disease. Abnormally activated and differentiated B cells may play important roles. Regulatory B cells (Breg) are newly defined B cell subgroups with immunosuppressive functions. In this study, we investigated the differences of B cell subsets, the expressions of co-stimulatory molecules on B cells, and the function of Breg cells in patients with IgG4-RD, primary Sjögren's syndrome (pSS) as well as in healthy controls (HC).
METHODS: Newly diagnosed IgG4-RD patients (n = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were recruited as disease and healthy controls. To analyze B cell subsets and B cell activity, PBMCs were surface stained and detected by flow cytometry. The function of Breg cells was tested by coculturing isolated CD19 + CD24(hi)CD38(hi) Breg cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA and cytometric bead array. Relationship between clinical data and laboratory findings were analyzed as well.
RESULTS: Compared with pSS patients and HC, IgG4-RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 + CD24-CD38(hi) B cell subsets were significantly higher in peripheral B cells from IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4 levels. The expression of BAFF-R and CD40 on B cells was significantly lower in IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg cells from pSS patients lacked suppressive functions.
CONCLUSIONS: B cells in patients with IgG4-RD and pSS display a variety of abnormalities, including disturbed B cell subpopulations, abnormal expression of key signaling molecules, co-stimulatory molecules, and inflammatory cytokines. In addition, a significantly increased B cell subset, CD19 + CD24-CD38(hi) B cells, may play an important role in the pathogenesis of IgG4-RD.
METHODS: Newly diagnosed IgG4-RD patients (n = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were recruited as disease and healthy controls. To analyze B cell subsets and B cell activity, PBMCs were surface stained and detected by flow cytometry. The function of Breg cells was tested by coculturing isolated CD19 + CD24(hi)CD38(hi) Breg cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA and cytometric bead array. Relationship between clinical data and laboratory findings were analyzed as well.
RESULTS: Compared with pSS patients and HC, IgG4-RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 + CD24-CD38(hi) B cell subsets were significantly higher in peripheral B cells from IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4 levels. The expression of BAFF-R and CD40 on B cells was significantly lower in IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg cells from pSS patients lacked suppressive functions.
CONCLUSIONS: B cells in patients with IgG4-RD and pSS display a variety of abnormalities, including disturbed B cell subpopulations, abnormal expression of key signaling molecules, co-stimulatory molecules, and inflammatory cytokines. In addition, a significantly increased B cell subset, CD19 + CD24-CD38(hi) B cells, may play an important role in the pathogenesis of IgG4-RD.
Предметные рубрики MeSH
ADP-ribosyl Cyclase 1AdultAgedAntigens, CD19Autoimmune DiseasesB-Cell Activation Factor ReceptorB-Lymphocyte SubsetsB-Lymphocytes, RegulatoryCD24 AntigenCD4-Positive T-LymphocytesCD40 AntigensCells, CulturedCytokinesEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHumansImmunoglobulin GInterleukin-2 Receptor alpha SubunitLeukocytes, MononuclearMaleMiddle AgedSjogren's Syndrome