2026-06-14T03:51:46Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/173732024-09-27T08:51:51Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc de Yébenes, Virginia G author Bartolomé-Izquierdo, Nahikari author Nogales-Cadenas, Rubén author Pérez-Durán, Pablo author Mur, Sonia M author Martínez, Nerea author Di Lisio, Lorena author Robbiani, Davide F author Pascual-Montano, Alberto author Cañamero, Marta author Piris, Miguel A author Ramiro, Almudena R author 2014-07-10 microRNAs 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. Blood. 2014 Jul 10;124(2):229-39. 10.1182/blood-2013-12-543611 1528-0020 Blood 24850757 http://hdl.handle.net/20.500.12105/17373 miR-217 is an oncogene that enhances the germinal center reaction.