微小 RNA 可防止自身反应性抗体的产生。
MicroRNAs prevent the generation of autoreactive antibodies.
机构信息
DNA Hypermutation and Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.
出版信息
Immunity. 2010 Nov 24;33(5):713-22. doi: 10.1016/j.immuni.2010.11.010.
Abstract
MicroRNAs have been shown to be critical for a number of aspects of immune system regulation and function. Here, we have examined the role of microRNAs in terminal B cell differentiation by analyzing Cd19-Cre(ki/+) Dicer1(fl/fl) mice. We found that in the absence of Dicer, the transitional and marginal zone (MZ) B cell compartments were overrepresented and follicular (FO) B cell generation was impaired. microRNA analysis revealed that miR185, a microRNA overexpressed in FO cells, dampened B cell receptor (BCR) signaling through Bruton tyrosine kinase downregulation. Dicer-deficient B cells had a skewed BCR repertoire with hallmarks of autoreactivity, which correlated with high titers of autoreactive antibodies in serum and autoimmune features in females. Together, our results reveal a crucial role for microRNAs in late B cell differentiation and in the establishment of B cell tolerance.
摘要
MicroRNAs 已被证明在免疫系统调节和功能的许多方面都至关重要。在这里，我们通过分析 Cd19-Cre(ki/+) Dicer1(fl/fl) 小鼠，研究了 microRNAs 在终末 B 细胞分化中的作用。我们发现，在没有 Dicer 的情况下，过渡区和边缘区 (MZ) B 细胞区室过度表达，滤泡 (FO) B 细胞生成受损。microRNA 分析表明，在 FO 细胞中过度表达的 microRNA-185 通过下调 Bruton 酪氨酸激酶来抑制 B 细胞受体 (BCR) 信号。缺乏 Dicer 的 B 细胞具有偏向性的 BCR repertoire，具有自身反应的特征，这与血清中自身反应性抗体的高滴度和雌性的自身免疫特征相关。总之，我们的研究结果揭示了 microRNAs 在晚期 B 细胞分化和 B 细胞耐受建立中的关键作用。
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