The RNase III enzyme Dicer is essential for germinal center B-cell formation.
Xu S , Guo K , Zeng Q , Huo J , Lam KP
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and are important for pre-B and follicular B lymphopoiesis as demonstrated respectively, by mb-1-Cre- and cd19-Cre-mediated deletion of Dicer, the RNase III enzyme critical for generating mature miRNAs. To explore the role of miRNAs in B cell terminal differentiation, we use Aicda-Cre to specifically delete Dicer in activated B cells where activation-induced cytidine deaminase (AID) is highly expressed. We demonstrate that mutant mice fail to produce high-affinity class-switched antibodies and generate memory B and long-lived plasma cells (PCs) upon immunization with a T cell-dependent antigen. More importantly, germinal center (GC) B cell formation is drastically compromised in the absence of Dicer, as a result of defects in cell proliferation and survival. Dicer-deficient GC B cells express higher levels of cell cycle inhibitor genes and proapoptotic protein Bim. Ablation of Bim could partially rescue the defect in GC B cell formation in Dicer-deficient mice. Taken together, our data suggest that Dicer and likely, miRNAs are critical for GC B cell formation during B cell terminal differentiation.
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