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MicroRNAs prevent the generation of autoreactive antibodies.

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.

journal_name

Immunity

journal_title

Immunity

authors

Belver L,de Yébenes VG,Ramiro AR

doi

10.1016/j.immuni.2010.11.010

subject

Has Abstract

pub_date

2010-11-24 00:00:00

pages

713-22

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(10)00416-4

journal_volume

33

pub_type

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