MiR-210 Is Induced by Oct-2, Regulates B Cells, and Inhibits Autoantibody Production
Mok Y., Schwierzeck V., Thomas DC., Vigorito E., Rayner TF., Jarvis LB., Prosser HM., Bradley A., Withers DR., Mårtensson I-L., Corcoran LM., Blenkiron C., Miska EA., Lyons PA., Smith KGC.
Abstract MicroRNAs (MiRs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we show that MiR-210 is induced by Oct-2, a key transcriptional mediator of B cell activation. Germline deletion of MiR-210 results in the development of autoantibodies from 5 mo of age. Overexpression of MiR-210 in vivo resulted in cell autonomous expansion of the B1 lineage and impaired fitness of B2 cells. Mice overexpressing MiR-210 exhibited impaired class-switched Ab responses, a finding confirmed in wild-type B cells transfected with a MiR-210 mimic. In vitro studies demonstrated defects in cellular proliferation and cell cycle entry, which were consistent with the transcriptomic analysis demonstrating downregulation of genes involved in cellular proliferation and B cell activation. These findings indicate that Oct-2 induction of MiR-210 provides a novel inhibitory mechanism for the control of B cells and autoantibody production.