microRNAs link the germinal center reaction with mature B cell lymphomagenesis

Ponente: Almudena Ramiro

Centro Nacional de Investigaciones Cardiovasculares (CNIC) [Madrid, Spain]

Host: Mercedes Dosil

Fecha:

Hora: 12:30

Salón de Actos del CIC

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. While 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 downregulates 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. In addition, we have recently identified a germinal center microRNA with tumor suppressor activity in non-hodgkin lymphoma. Our results link the germinal center with mature B cell lymphomagenesis.