title: miR-181b negatively regulates activation-induced cytidine deaminase in B cells.
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.
authors.affiliation: DNA Hypermutation and Cancer Group, Spanish National Cancer Research Center, Madrid 28029, Spain.
authors.forename: Virginia G
authors.initials: VG
authors.lastname: de Yébenes
authors.forename: Laura
authors.initials: L
authors.lastname: Belver
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.forename: Susana
authors.initials: S
authors.lastname: González
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Villasante
authors.forename: Carlo
authors.initials: C
authors.lastname: Croce
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Almudena R
authors.initials: AR
authors.lastname: Ramiro