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Updated: May 27, 2026

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
Published on: April 20, 2021
The RNase III enzyme Dicer is essential for germinal center B-cell formation
1Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore. xu_shengli@bti.a-star.edu.sg
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.
Insights
Dicer, essential for microRNAs (miRNAs), is crucial for germinal center B-cell formation and antibody production. Its absence impairs B-cell proliferation and survival, impacting immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression.
- Dicer is essential for miRNA maturation.
- Previous studies linked Dicer deletion to impaired B-cell development.
Purpose of the Study:
- To investigate the role of Dicer and miRNAs in B-cell terminal differentiation.
- To understand Dicer's function in activated B cells during immune responses.
Main Methods:
- Used Aicda-Cre mice to specifically delete Dicer in activated B cells.
- Immunized mice with a T cell-dependent antigen.
- Analyzed B-cell populations, antibody production, and gene expression.
Main Results:
- Dicer-deficient mice failed to produce high-affinity antibodies and generate memory B and plasma cells.
- Germinal center B-cell formation was severely compromised due to defects in proliferation and survival.
- Dicer-deficient GC B cells showed increased cell cycle inhibitors and Bim expression.
- Ablating Bim partially rescued GC B-cell formation defects.
Conclusions:
- Dicer and miRNAs are critical for germinal center B-cell formation.
- Dicer regulates B-cell proliferation and survival pathways.
- These findings highlight the importance of miRNA processing in adaptive immunity.
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