Epstein-Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease.
Epstein-Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease.
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DOI：
10.1089/vim.2016.0179
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发表时间：
2017-04
期刊：
影响因子：
2.2
通讯作者：
Hayashi K
中科院分区：
文献类型：
--
作者：
Nagata K;Kumata K;Nakayama Y;Satoh Y;Sugihara H;Hara S;Matsushita M;Kuwamoto S;Kato M;Murakami I;Hayashi K
格雷夫斯病是一种自身免疫性疾病，可导致甲状腺功能亢进，也是甲状腺功能亢进的最常见原因，B 淋巴细胞中持续存在的 Epstein-Barr 病毒 (EBV) 的重新激活会诱导宿主 B 细胞分化为浆细胞。我们之前报道过一些EBV感染的B细胞具有促甲状腺素受体抗体（TRAbs）作为表面免疫球蛋白（Igs），EBV再激活诱导这些TRAb+EBV+细胞产生TRAbs。 EBV 重新激活诱导宿主 B 细胞产生 Ig。本研究的目的是检测 B 细胞培养液中总 Ig 的产生，并检测 EBV 再激活诱导期间培养 B 细胞中激活诱导的胞苷脱氨酶 (AID)、核因子 kappa B (NF-κB) 和 EBV 潜伏膜蛋白 (LMP) 1，然后我们讨论了 EBV 再激活诱导的 Ig 产生与自身免疫相关的机制。我们发现 EBV 重新激活会诱导每种 Ig 同种型的产生，并表明 Ig 的产生是由 AID 通过 LMP1 和 NF-κB 催化的。 IgM 的量明显大于 IgG 的结果表明 LMP1 导致多克隆 B 细胞活化。我们提出了EBV再激活诱导Ig产生的途径；新感染 EBV 的 B 细胞通过多克隆 B 细胞激活而被激活，并通过 EBV 重新激活诱导的浆细胞分化产生 Igs。 LMP1 诱导的 AID 使 B 细胞能够进行类别转换重组，从而产生每种同种型的 Ig。根据这一机制，EBV拯救自身反应性B细胞以产生自身抗体，从而导致自身免疫性疾病的发展和恶化。
Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein–Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity. We showed that the EBV reactivation induces the production of every isotype of Ig and suggested that the Ig production was catalyzed by AID through LMP1 and NF-κB. The results that the amount of IgM was significantly larger compared with IgG suggested the polyclonal B cell activation due to LMP1. We proposed the pathway of EBV reactivation induced Ig production; B cells newly infected with EBV are activated by polyclonal B cell activation and produce Igs through plasma cell differentiation induced by EBV reactivation. LMP1-induced AID enabled B cells to undergo class-switch recombination to produce every isotype of Ig. According to this mechanism, EBV rescues autoreactive B cells to produce autoantibodies, which contribute to the development and exacerbation of autoimmune diseases.