MicroRNAs prevent the generation of autoreactive antibodies

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 margi...

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Vydáno v:Immunity (Cambridge, Mass.) Ročník 33; číslo 5; s. 713
Hlavní autoři: Belver, Laura, de Yébenes, Virginia G, Ramiro, Almudena R
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 24.11.2010
Témata:
Agammaglobulinaemia Tyrosine Kinase
Animals
Antigens, CD19 - genetics
Autoantibodies - biosynthesis
B-Lymphocytes - immunology
Cell Differentiation
DEAD-box RNA Helicases - genetics
Down-Regulation
Endoribonucleases - genetics
Female
Immune Tolerance
Lymphocyte Activation
Mice
Mice, Knockout
MicroRNAs - metabolism
Protein-Tyrosine Kinases - metabolism
Receptors, Antigen, B-Cell - metabolism
Ribonuclease III
ISSN:1097-4180, 1097-4180
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Shrnutí: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.
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2010.11.010