CD19 + CD24 hi CD38 hi B Cell Dysfunction in Primary Biliary Cholangitis.
MEDIATORS OF INFLAMMATION(2020)
摘要
CD19(+)CD24(hi)CD38(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(+)CD24(hi)CD38(hi)B cells in PBC is unknown. This study investigated the frequency and functional variation of circulating CD19(+)CD24(hi)CD38(hi)B cells in PBC patients. Flow cytometry was employed to quantify the percentage of CD19(+)CD24(hi)CD38(hi)B cells in peripheral blood samples. Correlations between CD19(+)CD24(hi)CD38(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(+)CD24(hi)CD38(hi)B cells from PBC patients were analyzed. The effect of CD19(+)CD24(hi)CD38(hi)B cells on CD4(+)T cell differentiation was evaluated. The percentage of CD19(+)CD24(hi)CD38(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(+)CD24(hi)CD38(hi)B cells from PBC patients. Moreover, Tim-1 levels were significantly downregulated in CD19(+)CD24(hi)CD38(hi)B cells from PBC patients. Coculture showed that PBC-derived CD19(+)CD24(hi)CD38(hi)B cells were less capable of CD4(+)T cell inhibition, but promoted Th1 cell differentiation. In conclusion, PBC patients have expanded percentages, but impaired CD19(+)CD24(hi)CD38(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.
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关键词
cholangitis,cd19<sup>+</sup>cd24<sup>hi</sup>cd38<sup>hi</sup>,cd19<sup>+</sup>cd24<sup>hi</sup>cd38<sup>hi</sup>,cd19<sup>+</sup>cd24<sup>hi</sup>cd38<sup>hi</sup>
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