Killer B lymphocytes and their fas ligand positive exosomes as inducers of immune tolerance.
Killer B lymphocytes and their fas ligand positive exosomes as inducers of immune tolerance.
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DOI：
10.3389/fimmu.2015.00122
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发表时间：
2015
影响因子：
7.3
通讯作者：
Fox DA
中科院分区：
文献类型：
--
作者：
Lundy SK;Klinker MW;Fox DA
免疫耐受的诱导是一个关键过程，通过该过程，免疫系统被训练以调节针对良性刺激（例如自身抗原和肠道微生物）的反应。了解和利用免疫耐受的自然机制可能成为治疗多种类型的过敏性和自身免疫性疾病以及提高实体器官移植接受度的越来越有用的策略。本实验室和其他实验室一直对某些B淋巴细胞表达死亡诱导分子Fas配体（FasL）的天然能力以及它们杀死T辅助（TH）淋巴细胞的能力感兴趣。我们最近表明，通过EB病毒（EBV）的非复制型变体对人B细胞进行实验性转化，始终导致功能性FasL蛋白的高表达。还观察到共表达主要组织相容性复合体（MHC）II类分子并具有杀死抗原特异性TH细胞的能力的FasL+外泌体的产生和释放。几条证据表明，FasL+ B细胞和FasL+MHCII+外泌体在天然免疫耐受中具有重要作用，并且具有很大的治疗潜力。综上所述，这些发现表明，EBV永生化的人B类淋巴母细胞系可用作FasL+外泌体的细胞工厂，其将用于治疗性地建立和/或恢复对特异性抗原的免疫耐受性。本文综述了FasL+ B细胞和外泌体在免疫调节中的作用，并提出了用于临床目的的操纵杀伤B细胞和FasL+外泌体的方法。
Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of allergic and autoimmune diseases, as well as for improving the acceptance of solid organ transplants. Our laboratory and others have been interested in the natural ability of some B lymphocytes to express the death-inducing molecule Fas ligand (FasL), and their ability to kill T helper (TH) lymphocytes. We have recently shown that experimental transformation of human B cells by a non-replicative variant of Epstein-Barr virus (EBV) consistently resulted in high expression of functional FasL protein. The production and release of FasL+ exosomes that co-expressed major histocompatibility complex (MHC) class II molecules and had the capacity to kill antigen-specific TH cells was also observed. Several lines of evidence indicate that FasL+ B cells and FasL+MHCII+ exosomes have important roles in natural immune tolerance and have a great deal of therapeutic potential. Taken together, these findings suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as cellular factories for FasL+ exosomes, which would be employed to therapeutically establish and/or regain immune tolerance toward specific antigens. The goals of this review are to summarize current knowledge of the roles of FasL+ B cells and exosomes in immune regulation, and to suggest methods of manipulating killer B cells and FasL+ exosomes for clinical purposes.
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影响因子：
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