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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...

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Autores principales: Chen, Qubo, Lai, Lanmin, Chi, Xiaoling, Lu, Xinyi, Wu, Huaxian, Sun, Jing, Wu, Weilin, Cai, Li, Zeng, Xuan, Wang, Chuyang, Chen, WeiCheng, Peng, Anping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
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
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author Chen, Qubo
Lai, Lanmin
Chi, Xiaoling
Lu, Xinyi
Wu, Huaxian
Sun, Jing
Wu, Weilin
Cai, Li
Zeng, Xuan
Wang, Chuyang
Chen, WeiCheng
Peng, Anping
author_facet Chen, Qubo
Lai, Lanmin
Chi, Xiaoling
Lu, Xinyi
Wu, Huaxian
Sun, Jing
Wu, Weilin
Cai, Li
Zeng, Xuan
Wang, Chuyang
Chen, WeiCheng
Peng, Anping
author_sort Chen, Qubo
collection PubMed
description 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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spelling pubmed-70355712020-02-26 CD19(+)CD24(hi)CD38(hi) B Cell Dysfunction in Primary Biliary Cholangitis Chen, Qubo Lai, Lanmin Chi, Xiaoling Lu, Xinyi Wu, Huaxian Sun, Jing Wu, Weilin Cai, Li Zeng, Xuan Wang, Chuyang Chen, WeiCheng Peng, Anping Mediators Inflamm Research Article 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. Hindawi 2020-02-10 /pmc/articles/PMC7035571/ /pubmed/32104147 http://dx.doi.org/10.1155/2020/3019378 Text en Copyright © 2020 Qubo Chen et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chen, Qubo
Lai, Lanmin
Chi, Xiaoling
Lu, Xinyi
Wu, Huaxian
Sun, Jing
Wu, Weilin
Cai, Li
Zeng, Xuan
Wang, Chuyang
Chen, WeiCheng
Peng, Anping
CD19(+)CD24(hi)CD38(hi) B Cell Dysfunction in Primary Biliary Cholangitis
title CD19(+)CD24(hi)CD38(hi) B Cell Dysfunction in Primary Biliary Cholangitis
title_full CD19(+)CD24(hi)CD38(hi) B Cell Dysfunction in Primary Biliary Cholangitis
title_fullStr CD19(+)CD24(hi)CD38(hi) B Cell Dysfunction in Primary Biliary Cholangitis
title_full_unstemmed CD19(+)CD24(hi)CD38(hi) B Cell Dysfunction in Primary Biliary Cholangitis
title_short CD19(+)CD24(hi)CD38(hi) B Cell Dysfunction in Primary Biliary Cholangitis
title_sort cd19(+)cd24(hi)cd38(hi) b cell dysfunction in primary biliary cholangitis
topic Research Article
url 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
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