The role of microRNA-142 in B cell activation and effector functions

Abstract

Abstract Control of gene expression by microRNA (miRNA) has recently emerged as a critical mechanism that regulates B cell activation and function. However, the role of specific miRNAs in this process is unclear. Using germline knockout (KO) mice, we have previously shown that miR-142 ablation impairs humoral immune responses despite significant expansion of the B cell compartment, suggesting that miR-142 is critical for B cell effector function and terminal differentiation. To more precisely dissect the role of miR 142 in B cell effector responses, we developed an activated B cell-specific miR-142 KO mouse by breeding conditional miR-142 KO (miR-142fl/fl) mice with mice expressing Cre recombinase driven by activation-induced cytosine deaminase (AIDcre). To label activated B cells in miR-142fl/fl AIDcre mice, we bred them to mice carrying a loxP-flanked STOP cassette, allowing for the expression of fluorescent Zsgreen1 reporter protein in the presence of Cre recombinase. As expected, B cell development was largely unperturbed in miR-142fl/fl AIDcreZsgreen+/− mice. In contrast, FACS analysis of naive and antigen-challenged miR-142fl/fl AIDcre Zsgreen+/− mice revealed a significant decrease in germinal center (GC) B cells and plasma cells (PCs). RNA sequencing of GC B cells suggests dysregulation of transcription factor networks such as miR-142-3p targets BACH2 and IRF4 may contribute to the phenotypes observed in miR 142fl/fl AIDcre Zsgreen+/− mice. Future experiments will investigate molecular pathways governing terminal B cell differentiation and effector function in miR-142fl/fl AIDcre Zsgreen+/− mice, thereby elucidating the role of miR-142 in promoting a healthy response to antigen.