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J Exp Med. 2008 Sep 29;205(10):2199-206. doi: 10.1084/jem.20080579. Epub 2008 Sep 1.

miR-181b negatively regulates activation-induced cytidine deaminase in B cells.

Author information

  • 1DNA Hypermutation and Cancer Group, Spanish National Cancer Research Center, Madrid 28029, Spain.

Abstract

Activated B cells reshape their primary antibody repertoire after antigen encounter by two molecular mechanisms: somatic hypermutation (SHM) and class switch recombination (CSR). SHM and CSR are initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues on the immunoglobulin loci, which leads to the generation of DNA mutations or double-strand break intermediates. As a bystander effect, endogenous AID levels can also promote the generation of chromosome translocations, suggesting that the fine tuning of AID expression may be critical to restrict B cell lymphomagenesis. To determine whether microRNAs (miRNAs) play a role in the regulation of AID expression, we performed a functional screening of an miRNA library and identified miRNAs that regulate CSR. One such miRNA, miR-181b, impairs CSR when expressed in activated B cells, and results in the down-regulation of AID mRNA and protein levels. We found that the AID 3' untranslated region contains multiple putative binding sequences for miR-181b and that these sequences can be directly targeted by miR-181b. Overall, our results provide evidence for a new regulatory mechanism that restricts AID activity and can therefore be relevant to prevent B cell malignant transformation.

PMID:
18762567
[PubMed - indexed for MEDLINE]
PMCID:
PMC2556787
Free PMC Article
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