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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activation of naive B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders.
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Activation of naive B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders.

机译：通过CD81激活幼稚B淋巴细胞，这是丙型肝炎病毒相关B淋巴细胞疾病的发病机制。

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摘要

Infection with hepatitis C virus (HCV), a leading cause of chronic liver diseases, can associate with B lymphocyte proliferative disorders, such as mixed cryoglobulinemia and non-Hodgkin lymphoma. The major envelope protein of HCV (HCV-E2) binds, with high affinity CD81, a tetraspanin expressed on several cell types. Here, we show that engagement of CD81 on human B cells by a combination of HCV-E2 and an anti-CD81 mAb triggers the JNK pathway and leads to the preferential proliferation of the naive (CD27-) B cell subset. In parallel, we have found that B lymphocytes from the great majority of chronic hepatitis C patients are activated and that naive cells display a higher level of activation markers than memory (CD27+) B lymphocytes. Moreover, eradication of HCV infection by IFN therapy is associated with normalization of the activation-markers expression. We propose that CD81-mediated activation of B cells in vitro recapitulates the effects of HCV binding to B cell CD81 in vivo and that polyclonal proliferation of naive B lymphocytes is a key initiating factor for the development of the HCV-associated B lymphocyte disorders.
机译：丙型肝炎病毒（HCV）感染是慢性肝病的主要原因，可与B淋巴细胞增生性疾病（例如混合性冷球蛋白血症和非霍奇金淋巴瘤）相关。 HCV的主要包膜蛋白（HCV-E2）以高亲和力CD81结合在几种细胞类型上表达的四跨膜蛋白。在这里，我们显示通过HCV-E2和抗CD81 mAb的组合，CD81在人B细胞上的参与会触发JNK途径并导致幼稚（CD27-）B细胞亚群的优先增殖。同时，我们发现绝大多数慢性丙型肝炎患者的B淋巴细胞均被激活，并且幼稚细胞显示出比记忆（CD27 +）B淋巴细胞更高水平的激活标记。此外，通过IFN疗法根除HCV感染与激活标志物表达的正常化有关。我们建议，CD81介导的B细胞体外激活在体内概括了HCV与B细胞CD81结合的作用，并且幼稚B淋巴细胞的多克隆增殖是HCV相关B淋巴细胞疾病发展的关键起始因素。

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