| First Author | Xu S | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 3 | Pages | 767-76 |
| PubMed ID | 22117047 | Mgi Jnum | J:181782 |
| Mgi Id | MGI:5314174 | Doi | 10.1182/blood-2011-05-355412 |
| Citation | Xu S, et al. (2012) The RNase III enzyme Dicer is essential for germinal center B-cell formation. Blood 119(3):767-76 |
| abstractText | 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. |
