Immune tolerance induced by avian leukosis virus subgroup J (ALV-J) is a prerequisite for tumorigenesis. Although we had reported that B cell anergy induced by ALV-J was the main reason for immune tolerance, the molecular mechanism still remains unclear. Here, we found SU protein of ALV-J interacted with tyrosine kinase Lyn (a key protein in BCR signaling pathway) by confocal laser scanning microscopy and co-immunoprecipitation test, which suggested that Lyn might play an important role in B cell anergy induced by ALV-J. Correspondingly, the mRNA and protein level of Lyn was significantly up-regulated in B cells after ALV-J infection. Subsequently, the phosphorylated protein levels of Lyn at Tyr507 site were significantly up-regulated in ALV-J-infected B cells after BCR signal activation, but the phosphorylated protein level of Syk (a direct substrate of Lyn) at Tyr525/526 site, Ca²⁺ flux, and NF-κB p65 protein level were significantly down-regulated. Interestingly, the phosphorylated protein level of Syk at Tyr525/526 site, Ca²⁺ flux, and NF-κB p65 protein level were both significantly retrieved after the shLyn treatment in B cells infected by ALV-J. In summary, these results indicated that ALV-J activated the negative regulatory effect of phosphorylated Lyn protein at 507 site in BCR signal transduction pathway and then mediated B cell anergy, which will provide a new insight for revealing the pathogenesis of immune tolerance induced by ALV-J.

禽白血病病毒J亚组（ALV-J）诱导的免疫耐受是肿瘤发生的先决条件。尽管我们已经报道了ALV-J诱导的B细胞无反应是免疫耐受的主要原因，但其分子机制仍然不清楚。在这里，我们通过共聚焦激光扫描显微镜和免疫共沉淀试验发现了ALV-J的SU蛋白与酪氨酸激酶Lyn（BCR信号通路中的关键蛋白）相互作用，这表明Lyn可能在由B诱导的B细胞无能中起重要作用。 ALV-J。相应地，ALV-J感染后，B细胞中Lyn的mRNA和蛋白水平显着上调。随后，在BCR信号激活后，ALV-J感染的B细胞中Tyr507位点Lyn的磷酸化蛋白水平显着上调，²⁺通量和NF-κBp65蛋白水平显着下调。有趣的是，shLyn处理后，在ALV-J感染的B细胞中，Tyr525 / 526位点的Syk磷酸化蛋白水平，Ca ²⁺通量和NF-κBp65蛋白水平均显着恢复。总之，这些结果表明，ALV-J激活了BCR信号转导途径中507位磷酸化Lyn蛋白的负调控作用，然后介导了B细胞无反应，这将为揭示ALV诱导的免疫耐受的发病机理提供新的见解。 -J