The RNase III enzyme Dicer is essential for germinal center B-cell formation

• Published in: Blood Vol. 119; no. 3; pp. 767 - 776
• Main Authors: Xu, Shengli, Guo, Ke, Zeng, Qi, Huo, Jianxin, Lam, Kong-Peng
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 19.01.2012; Americain Society of Hematology
• Subjects: Animals; Apoptosis; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; Biological and medical sciences; Cell Differentiation; Cell Proliferation; Cytidine Deaminase - physiology; DEAD-box RNA Helicases - physiology; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Germinal Center - cytology; Germinal Center - metabolism; Hematologic and hematopoietic diseases; Immunization; Immunologic Memory; Integrases - metabolism; Male; Medical sciences; Mice; Mice, Knockout; Plasma Cells - immunology; Plasma Cells - metabolism; Ribonuclease III - physiology; RNA Editing; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Gene silencing; RNA interference; Hematology; Enzyme; Germinative center; Hydrolases; Esterases; B-Lymphocyte; Germinal cell; Pancreatic ribonuclease
• DOI: 10.1182/blood-2011-05-355412
• ISSN: 0006-4971

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.