Abstract
Apoptosis induced by B-cell receptor (BCR) signaling is critical for antigen-driven selection, a process critical to tolerance and immunity. Here, we examined the roles of microRNAs (miRNAs) in BCR signaling-induced apoptosis using the widely applied WEHI-231 model. Comparison of miRNA levels in BCR-stimulated and -unstimulated cells revealed that 39 miRNAs were differentially expressed upon stimulation of the BCR. Importantly, stimulation in the presence of anti-CD40 antibodies, which rescues cells from BCR-induced apoptosis, prevented most changes in miRNA expression. Ectopic expression of mir-150 and mir-181a1b1, miRNAs that were upregulated upon BCR stimulation, resulted in inhibition of cell growth. Finally, we showed that ectopic expression of mir-150, mir-181a1b1 and mir-17∼92 sensitized cells to anti-IgM stimulation-induced growth inhibition. Together, these results demonstrate that miRNAs are involved in BCR signaling, suggesting that they may have important roles in the regulation of B cell-mediated tolerance and immunity.
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Acknowledgements
We thank members of the Chen Lab and the van den Berg Lab for helpful discussions and advice, Dr David Hirschberg and Gergana Nestorova for their excellent advice and assistance with the miRNA microarray profiling, and Prof Dr Anke van den Berg and Dr Bart-Jan Kroesen for critical reading of the manuscript. This work was supported by an NWO Rubicon fellowship (825.06.027, JK) and NIH grants (1R01AI073724 and 1DP1 OD00643501, CZC) and a W.M. Keck young scholar award (CZC).
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Kluiver, J., Chen, CZ. MicroRNAs regulate B-cell receptor signaling-induced apoptosis. Genes Immun 13, 239–244 (2012). https://doi.org/10.1038/gene.2012.1
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DOI: https://doi.org/10.1038/gene.2012.1
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