Possible Recruitment of Peripheral Blood CXCR3+ CD27+ CD19+ B Cells to the Liver of Chronic Hepatitis C Patients

Possible Recruitment of Peripheral Blood CXCR3+ CD27+ CD19+ B Cells to the Liver of Chronic Hepatitis C Patients
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DOI:
10.1089/jir.2009.0047
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发表时间:
2010-04-01
影响因子:
2.3
通讯作者:
Yamaguchi, Kazunari
Yamaguchi, Kazunari
中科院分区:
医学4区
文献类型:
--
作者:
Mizuochi, Toshiaki;Ito, Masahiko;Yamaguchi, Kazunari

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已经提出丙型肝炎病毒(HCV)不仅感染肝细胞,而且感染免疫细胞,包括B细胞。B细胞的HCV感染可能是B细胞失调性疾病的原因,例如混合性冷球蛋白血症、类风湿因子产生和B细胞淋巴增生性疾病,其可能演变成非霍奇金淋巴瘤。为了阐明慢性HCV感染对B细胞动力学的影响,对慢性丙型肝炎患者(CHC)的外周B细胞进行了表征。我们发现CHC患者外周血中CD 27(+)B细胞的频率,即记忆表型,显著降低。同时,CHC血浆中IFN-γ诱导蛋白-10(IP-10)(CXCR 3配体)的量显著升高。此外,发现CD 27(+)B细胞群在CHC中高度表达CXCR 3,因此表明CD 27(+)B细胞群从外周血募集到CHC肝脏的炎症部位,在那里产生IP-10。肝内淋巴细胞免疫组化染色显示CXCR 3(+)B细胞浸润于CHC肝内。因此,我们的研究结果提供了新的见解记忆B细胞在HCV发病机制中的作用。
It has been suggested that hepatitis C virus (HCV) infects not only hepatocytes but also immune cells, including B cells. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma. To clarify the effects of chronic HCV infection on B-cell dynamics, peripheral B cells from chronic hepatitis C patients (CHC) were characterized. We found that the frequency of CD27(+) B cells, that is memory phenotype, was significantly reduced in the peripheral blood of CHC. At the same time, the amount of IFN-gamma-inducible protein-10 (IP-10), a CXCR3 ligand, was markedly elevated in the plasma of CHC. Furthermore, the CD27(+) B-cell population was found to highly express CXCR3 in CHC, thus suggesting that the CD27(+) B-cell population was recruited from peripheral blood to the inflammatory site of the liver of CHC, where IP-10 is produced. Immunohistochemical analyses of intrahepatic lymphocytes indicated that CXCR3(+) B cells were infiltrated in the liver of CHC. Our results thus offer new insight into the role of memory B cells in the HCV pathogenesis.