MicroRNAs regulate B-cell receptor signaling-induced apoptosis

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. © 2012 Macmillan Publishers Limited All rights reserved.