de Yébenes, Virginia GBartolomé-Izquierdo, NahikariNogales-Cadenas, RubénPérez-Durán, PabloMur, Sonia MMartínez, NereaDi Lisio, LorenaRobbiani, Davide FPascual-Montano, AlbertoCañamero, MartaPiris, Miguel ARamiro, Almudena R2024-01-252024-01-252014-07-10Blood. 2014 Jul 10;124(2):229-39.http://hdl.handle.net/20.500.12105/17373microRNAs are a class of regulators of gene expression that have been shown critical for a great number of biological processes; however, little is known of their role in germinal center (GC) B cells. Although the GC reaction is crucial to ensure a competent immune response, GC B cells are also the origin of most human lymphomas, presumably due to bystander effects of the immunoglobulin gene remodeling that takes place at these sites. Here we report that miR-217 is specifically upregulated in GC B cells. Gain- and loss-of-function mouse models reveal that miR-217 is a positive modulator of the GC response that increases the generation of class-switched antibodies and the frequency of somatic hypermutation. We find that miR-217 down-regulates the expression of a DNA damage response and repair gene network and in turn stabilizes Bcl-6 expression in GC B cells. Importantly, miR-217 overexpression also promotes mature B-cell lymphomagenesis; this is physiologically relevant as we find that miR-217 is overexpressed in aggressive human B-cell lymphomas. Therefore, miR-217 provides a novel molecular link between the normal GC response and B-cell transformation.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/AnimalsB-LymphocytesCell Transformation, NeoplasticCells, CulturedDNA DamageDNA RepairGene Regulatory NetworksGerminal CenterLymphomaMiceMice, TransgenicMicroRNAsMicroarray AnalysisOncogenesProto-Oncogene Proteins c-bcl-6Attribution-NonCommercial-NoDerivatives 4.0 Internacional24850757124222910.1182/blood-2013-12-5436111528-0020Bloodopen access