MicroRNAs prevent the generation of autoreactive antibodies.

MicroRNAs prevent the generation of autoreactive antibodies.
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DOI:
10.1016/j.immuni.2010.11.010
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发表时间:
2010-11-24
期刊:
影响因子:
32.4
通讯作者:
Ramiro AR
Ramiro AR
中科院分区:
医学1区
文献类型:
--
作者:
Belver L;de Yébenes VG;Ramiro AR

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MicroRNAs已被证明对免疫系统调节和功能的许多方面至关重要。在这里,我们通过分析CD19-Creki/+Dicerfl/fl小鼠,研究了microRNAs在B细胞终末分化中的作用。我们发现,在没有迪格尔的情况下,过渡区和边缘区(MZ)B细胞隔间的表达过度,滤泡(FO)B细胞的生成受到损害。MicroRNA分析表明,在FO细胞中过表达的miR185通过BTK下调抑制BCR信号。DICER缺陷B细胞具有偏斜的BCR谱系,具有自身反应的特征,这与血清中高滴度的自身反应抗体和女性的自身免疫特征有关。综上所述,我们的结果揭示了microRNAs在晚期B细胞分化和建立B细胞耐受性中的关键作用。
MicroRNAs have been shown 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 analysing Cd19-Creki/+ Dicerfl/fl mice. We found that in the absence of Dicer the transitional and marginal zone (MZ) B cell compartments are overrepresented, and follicular (FO) B cell generation is impaired. microRNA analysis reveals that miR185, a microRNA overexpressed in FO cells, dampens BCR signalling through Btk downregulation. Dicer deficient B cells have a skewed BCR repertoire with hallmarks of autoreactivity, which correlates with high titers of autoreactive antibodies in serum and autoimmune features in females. Together, our results reveal a crucial role of microRNAs in late B cell differentiation and in the establishment of B cell tolerance.
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