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CD19+CD24hiCD38hi B Cell Dysfunction in Primary Biliary Cholangitis.


ABSTRACT: CD19+CD24hiCD38hi 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+CD24hiCD38hi B cells in PBC is unknown. This study investigated the frequency and functional variation of circulating CD19+CD24hiCD38hi B cells in PBC patients. Flow cytometry was employed to quantify the percentage of CD19+CD24hiCD38hi B cells in peripheral blood samples. Correlations between CD19+CD24hiCD38hi B cells and routine laboratory parameters were assessed. Levels of IL-10, TNF-?, IL-6 and IL-12, and Tim-1 in CD19+CD24hiCD38hi B cells from PBC patients were analyzed. The effect of CD19+CD24hiCD38hi B cells on CD4+T cell differentiation was evaluated. The percentage of CD19+CD24hiCD38hi 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+CD24hiCD38hi B cells from PBC patients. Moreover, Tim-1 levels were significantly downregulated in CD19+CD24hiCD38hi B cells from PBC patients. Coculture showed that PBC-derived CD19+CD24hiCD38hi 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+CD24hiCD38hi 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.

SUBMITTER: Chen Q 

PROVIDER: S-EPMC7035571 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> B Cell Dysfunction in Primary Biliary Cholangitis.

Chen Qubo Q   Lai Lanmin L   Chi Xiaoling X   Lu Xinyi X   Wu Huaxian H   Sun Jing J   Wu Weilin W   Cai Li L   Zeng Xuan X   Wang Chuyang C   Chen WeiCheng W   Peng Anping A  

Mediators of inflammation 20200210


CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> 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>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> B cells in PBC i  ...[more]

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