[CD24.sup.hi][CD38.sup.hi] B Cell Dysfunction in Primary Biliary Cholangitis

• Published in: Mediators of inflammation Vol. 2019
• Main Authors: Chen, Qubo, Lai, Lanmin, Chi, Xiaoling, Lu, Xinyi, Wu, Huaxian, Sun, Jing, Wu, Weilin, Cai, Li, Zeng, Xuan, Wang, Chuyang, Chen, WeiCheng, Peng, Anping
• Format: Journal Article
• Language: English
• Published: John Wiley & Sons, Inc 01.03.2020
• Subjects: B cells; Ethylenediaminetetraacetic acid; T cells; China
• ISSN: 0962-9351
• DOI: 10.1155/2020/3019378

[CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells are immature transitional B cells that, in normal individuals, exert suppressive effects by IL-10 production but are quantitatively altered and/or functionally impaired in individuals with various autoimmune diseases. Primary biliary cholangitis (PBC), an autoimmune disease, clinically presents as chronic cholestasis and nonsuppurative destructive cholangitis. A role for [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells in PBC is unknown. This study investigated the frequency and functional variation of circulating [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells in PBC patients. Flow cytometry was employed to quantify the percentage of [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells in peripheral blood samples. Correlations between [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells and routine laboratory parameters were assessed. Levels of IL-10, TNF-[alpha], IL-6 and IL-12, and Tim-1 in [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells from PBC patients were analyzed. The effect of [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells on [CD4.sup.+]T cell differentiation was evaluated. The percentage of [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells in PBC patients was significantly higher than in healthy controls and was positively correlated with liver cholestasis. After activation by anti-B cell receptor and CpG, the production of IL-10 was decreased and the production of IL-6 and IL-12 was increased in [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells from PBC patients. Moreover, Tim-1 levels were significantly downregulated in [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells from PBC patients. Coculture showed that PBC-derived [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells were less capable of [CD4.sup.+]T cell inhibition, but promoted Th1 cell differentiation. In conclusion, PBC patients have expanded percentages, but impaired [CD19.sup.+][CD24.sup.hi][CD38.sup.hi] B cells, which correlate with disease damage. In PBC patients, this B cell subset has a skewed proinflammatory cytokine profile and a decreased capacity to suppress immune function, which may contribute to the pathogenesis of PBC.