MicroRNAs Prevent the Generation of Autoreactive Antibodies

被引：133

作者：

Belver, Laura ^{[1
]}

de Yebenes, Virginia G. ^{[1
]}

Ramiro, Almudena R. ^{[1
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, DNA Hypermutat & Canc Grp, Madrid 28029, Spain

来源：

IMMUNITY | 2010年 / 33卷 / 05期

基金：

欧洲研究理事会;

关键词：

BRUTONS TYROSINE KINASE; REACTIVE B-LYMPHOCYTES; MARGINAL-ZONE; CELL DEVELOPMENT; TRANSGENIC MICE; ACTIVATION; EXPRESS; POLYREACTIVITY; TOLERANCE; SELECTION;

D O I：

10.1016/j.immuni.2010.11.010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：713 / 722

页数：10

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