期刊
BLOOD
卷 124, 期 2, 页码 229-239出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-12-543611
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资金
- Ministerio de Economia y Competitividad
- Spanish National Cardiovascular Research Centre
- Juan de la Cierva research program
- Ministerio de Economia y Competitividad [SAF2010-21394]
- European Research Council [BCLYM-207844]
- Ministerio de Ciencia e Innovacion [BIO2010-17527]
- Government of Madrid [P2010/BMD-2305]
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.
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