MicroRNAs (miRNAs) are short noncoding 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 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 on 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 probably miRNAs are critical for GC B-cell formation during B-cell terminal differentiation.
Pubmed ID: 22117047 RIS Download
Mesh terms: Animals | Apoptosis | B-Lymphocytes | Cell Differentiation | Cell Proliferation | Cytidine Deaminase | DEAD-box RNA Helicases | Enzyme-Linked Immunosorbent Assay | Female | Flow Cytometry | Germinal Center | Immunization | Immunologic Memory | Integrases | Male | Mice | Mice, Knockout | Plasma Cells | RNA Editing | Ribonuclease III | T-Lymphocytes
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