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CD19(+)CD24(hi)CD38(hi) B Cell Dysfunction in Primary Biliary Cholangitis
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 d...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035571/ https://www.ncbi.nlm.nih.gov/pubmed/32104147 http://dx.doi.org/10.1155/2020/3019378 |
Sumario: | 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-α, 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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