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 immunity despite significant expansion of the B cell compartment, suggesting that miR-142 is critical for B cell effector function. We found that mice lacking miR-142 cannot generate specific antibody responses upon antigen challenge and display impaired germinal center (GC) formation and plasma cell 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). AID is required for class switch recombination and somatic hypermutation, and is induced in B cells upon antigen encounter. To label activated B cells in miR-142fl/flAIDCre mice, we bred them to Ai6 mice that carry a loxP-flanked STOP cassette, allowing for the expression of fluorescent ZsGreen1 reporter protein in the presence of Cre recombinase. FACS analysis of Peyer’s patches from naive miR-142fl/flAIDCreZsgreen+/− mice revealed a significant decrease in GC B cells, while the number of ZsGreen1+ activated B cells increased, suggesting an aberrant B cell activation and GC response. We will discuss at the meeting the role of miR-142 in promoting humoral responses to antigen by presenting the findings from our ongoing studies of B cell differentiation and effector function in immunized miR-142fl/flAIDCreZsgreen+/− mice.