CD19+CD24hiCD38hi B Cell Dysfunction in Primary Biliary Cholangitis.

Qubo Chen,Anping Peng,Lanmin Lai,Weilin Wu,Li Cai,Xuan Zeng,Weicheng Chen,Xiaoling Chi,Jing Sun,Chuyang Wang,Huaxian Wu,Xinyi Lu

doi:10.1155/2020/3019378

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-α, 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.

Highlights

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that is characterized by a gradual loss of small bile ducts
PBC patients were diagnosed according to the Clinical Practice Guidelines by the European Association for the Study of the Liver (EASL) [28]: all individuals were subjected to the elevated serum alkaline phosphatase (ALP) and the presence of antimitochondrial antibody (AMA and AMA type M2) in serum
To assess the potential link between this subset and disease, CD19+CD24hiCD38hi B cells were correlated with clinical liver function indicators and clinical stages in PBC patients

Summary

Introduction

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that is characterized by a gradual loss of small bile ducts. The pathogenesis of PBC is not well understood Both autoimmune and inflammatory mechanisms have been described for PBC [1]. Despite high levels of antimitochondrial antibody (AMA), high levels of serum IgM, and the presence of infiltrating B cells in liver portal areas of PBC patients, a role for B cells in PBC has not been well identified [2,3,4,5]. Previous investigations have primarily concentrated on autoantibody-producing B cells, with few investigations of regulatory B cells (Breg). Lack or loss of IL-10-producing Breg exacerbates many autoimmune and inflammatory diseases, including arthritis, lupus, chronic colitis, and experimental autoimmune

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Conclusion