title: The RNase III enzyme Dicer is essential for germinal center B-cell formation.
abstract: 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.
authors: Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore. xu_shengli@bti.a-star.edu.sg
authors: Shengli
authors: S
authors: Xu
authors: Ke
authors: K
authors: Guo
authors: Qi
authors: Q
authors: Zeng
authors: Jianxin
authors: J
authors: Huo
authors: Kong-Peng
authors: KP
authors: Lam
mesh_terms: D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003564:Cytidine Deaminase / Q000502:physiology*; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology* / Q000378:metabolism; D007114:Immunization; D007156:Immunologic Memory; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D017393:RNA Editing; D043244:Ribonuclease III / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C045073:Cre recombinase; D019426:Integrases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D053487:DEAD-box RNA Helicases