Analysis of B-lymphocyte differentiation in patients infected with hepatitis C virus

Analysis of B-lymphocyte differentiation in patients infected with hepatitis C virus
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DOI:
10.1002/jmv.20039
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发表时间:
2004-04-01
影响因子:
12.7
通讯作者:
Inchauspé, G
Inchauspé, G
中科院分区:
医学3区
文献类型:
--
作者:
Fournillier, A;Freida, D;Inchauspé, G

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为了弄清丙型肝炎病毒(HCV)感染是否会影响B淋巴细胞的某些功能,研究了丙型肝炎病毒感染患者B淋巴细胞的表型特征及其向免疫球蛋白(Ig)分泌细胞分化的能力。在体外刺激金黄色葡萄球菌菌株Cowan I有丝分裂原后,研究了未经治疗和无反应(n = 9)、治疗和无反应(n = 6)、反应(n = 6)、长期反应(n = 9)以及血清阴性对照(n = 14)的B淋巴细胞分化情况。采用RT-PCR检测纯化的B淋巴细胞HCV序列。研究发现,与对照组相比,hcv患者B细胞的平均百分比和正常初始B细胞水平相似(未治疗无应答者IgM(+)/ IgD(+)细胞% = 79.7 +/- 15.4,治疗无应答者57.1 +/- 22.9,应答者44.3 +/- 29.1,长期应答者75.7 +/- 16)。研究还发现,患者或对照组的外周血单核细胞(PBMCs)在体外产生相似数量的IgG、A和M。57%未经治疗的无反应者和17%接受治疗的无反应者能够产生hcv特异性抗体。有趣的是,能够分泌抗HCV抗体的pbmc的B淋巴细胞含有HCV阳性链RNA,尽管没有发现系统检测到阴性链。这些数据表明,hcv感染患者的B淋巴细胞中通过B细胞受体(BCR)的信号传导似乎正常,无论他们对治疗的反应如何。分泌hcv特异性IgG的能力似乎与正链RNA的存在有关,而不是与病毒复制有关。(C) 2004 Wiley-Liss, Inc。
To clarify whether some of the functions of B lymphocytes could be affected during hepatitis C virus (HCV) infection, phenotypic characteristics of B lymphocytes from HCV-infected patients and their capacity to differentiate into immunoglobulins (Ig)-secreting cells were studied. B lymphocytes differentiation was investigated for patients untreated and non-responders (n = 9), treated and non-responders (n = 6), responders (n = 6), long-term responders (n = 9) to therapy and seronegative controls (n = 14) following in vitro stimulation with S. aureus strain Cowan I mitogen. HCV sequences in purified B lymphocytes were detected by RT-PCR. It was found that HCV-patients harbor a similar mean percentage of B cells and a normal level of naive B cells (% IgM(+)/ IgD(+) cells = 79.7 +/- 15.4 for untreated non-responders, 57.1 +/- 22.9 for treated non-responders, 44.3 +/- 29.1 for responders, 75.7 +/- 16 for long-term responders) as compared with controls. It was also found that peripheral blood mononuclear cells (PBMCs) of patients or controls produced similar amounts of IgG, A, and M in vitro. A total of 57% of untreated non-responders versus 17% of treated non-responders were able to produce HCV-specific antibodies. Interestingly, B lymphocytes from PBMCs able to secrete anti-HCV antibodies contained HCV positive strand RNA, although no systematic detection of the negative strand was found. These data suggest that signaling through the B cell receptor (BCR) in B lymphocytes of HCV-infected patients appears normal whatever their response to therapy. The capacity to secrete HCV-specific IgG seemed to be linked to the presence of positive strand RNA rather than virus replication. (C) 2004 Wiley-Liss, Inc.