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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Phosphorothioate-modified CpG oligodeoxynucleotides mimic autoantigens and reveal a potential role for Toll-like receptor 9 in receptor revision
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Phosphorothioate-modified CpG oligodeoxynucleotides mimic autoantigens and reveal a potential role for Toll-like receptor 9 in receptor revision

机译：硫代磷酸酯修饰的CpG寡脱氧核苷酸模仿自身抗原，并揭示Toll样受体9在受体修订中的潜在作用

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摘要

Re-expression of recombinase activating genes (RAG) in mature B cells may support autoreactivity by enabling revision of the B-cell receptor (BCR). Recent reports suggest that administration of Toll-like receptor 9 (TLR9) -stimulating CpG oligodeoxynucleotides (ODN) could trigger the manifestation of autoimmune disease and that TLR are involved in the selection processes eliminating autoreactive BCR. The mechanisms involved remain to be elucidated. This prompted us to ask, whether TLR9 could be involved in receptor revision. We found that phosphorothioate-modified CpG ODN (CpGPTO) induced expression of Ku70 and re-expression of RAG-1 in human peripheral blood B lymphocytes and Igλ expression in sorted Igκ+ B cells. Further results revealed unselective binding specificity of CpGPTO-induced immunoglobulin and suggested that CpGPTO engage and/or mimic IgM receptor signalling, an important prerequisite for the initialization of receptor editing or revision. Altogether, our data describe a potential role for TLR9 in receptor revision and suggest that CpGPTO could mimic chromatin-bearing autoantigens by simultaneously engaging the BCR and TLR9 on IgM+ B cells.
机译：在成熟的B细胞中重组酶激活基因（RAG）的重新表达可能通过使B细胞受体（BCR）得以修饰而支持自身反应性。最近的报道表明，施用刺激Toll样受体9（TLR9）的CpG寡脱氧核苷酸（ODN）可以触发自身免疫疾病的表现，并且TLR参与了选择过程，从而消除了自身反应性BCR。涉及的机制还有待阐明。这促使我们问，TLR9是否可能参与受体修订。我们发现硫代磷酸酯修饰的CpG ODN（CpGPTO）诱导人外周血B淋巴细胞中Ku70的表达和RAG-1的重新表达，以及分选的Igκ+ B细胞中的Igλ的表达。进一步的结果显示了CpGPTO诱导的免疫球蛋白的非选择性结合特异性，并提示CpGPTO参与和/或模仿IgM受体信号传导，这是初始化受体编辑或修订的重要前提。总而言之，我们的数据描述了TLR9在受体修订中的潜在作用，并暗示CpGPTO可以通过同时将BCR和TLR9结合在IgM + B细胞上来模拟带有染色质的自身抗原。

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