Regulation of B- and T-cell differentiation by a single microRNA.
miRs (microRNAs) post-transcriptionally regulate gene expression mainly by repressing translation or by inducing mRNA degradation. Dicer, an enzyme responsible for miR biogenesis, is required for T-cell function, suggesting regulatory roles for miRs in lymphocytes. However, specific roles for individual miRs are only just beginning to emerge. miR-155 is encoded within an exon of the non-coding RNA known as bic (B-cell integration cluster) and high levels of bic expression are induced upon antigen receptor stimulation of B- and T-cells, as well as TLR (Toll-like receptor) stimulation of macrophages and dendritic cells. High levels of bic/miR-155 are found in B-cell lymphomas and solid tumours, indicating that this locus may also be linked to cancer. Indeed, transgenic mice overexpressing miR-155 develop B-cell malignancies. To define the in vivo role of bic/miR-155 (bic), we have studied bic-deficient mice. These mice are immunodeficient and fail to generate high levels of class-switched antibody upon immunization with thymus-dependent and thymus-independent antigens. This defect is intrinsic to B-cells and manifested at the level of differentiation of switched plasmablasts into mature antibody secreting plasma cells. In addition, bic-deficient T-cells show skewed differentiation into the Th2 lineage under a variety of in vitro culture conditions. Microarray analysis of bic-deficient B- and T-cells under different conditions has revealed a wide spectrum of targets regulated by an miR-155 and suggested mechanisms for the regulation of lymphocyte differentiation by a single miR.
Turner
Martin
M
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK. martin.turner@bbsrc.ac.uk
Vigorito
Elena
E
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D017578:Immunoglobulin Class Switching; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000166:cytology*
D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse