ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Histone deacetylase inhibitors upregulate B cell microRNAs that silence AID and Blimp-1 expression for epigenetic modulation of antibody and autoantibody responses.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis.Frontiers in immunology · 2023Pooled it
- Epigenetic regulation of humoral immunity: molecular mechanisms, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- B cell TET2 recruits OGT for nuclear TET2 and H2B O-GlcNAcylation to drive AID and BLIMP-1 expression and maturation of the antibody response.Cell reports · 2026Article
- Short-, medium-, versus long-chain fatty acids: mechanisms of immunomodulation and disease pathogenesis.Cellular & molecular immunology · 2026Review
- Bifidobacterium-driven immunoglobulin A production in pediatric patients with IgA deficiency and recurrent respiratory tract infections.Microbiome · 2026Article
- UPLC-MS/MS-based metabolomics analysis identifies disease-associated metabolic signatures of B cells from patients with IgG4-RD.Frontiers in immunology · 2026Article
- Recent advances in the positive role ofFrontiers in immunology · 2026Review
- Microbiota-derived metabolites in hematopoietic regulation and disease: mechanisms, context, and therapeutic perspectives.Frontiers in microbiology · 2026Review
- Microbiota-driven epigenetic programming of local immunity.Frontiers in immunology · 2026Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity.Nature communications · 2025Article
- The role of fatty acid metabolism on B cells and B cell-related autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Gut Microbiota Mediates Neuroinflammation in Alzheimer's Disease: Unraveling Key Factors and Mechanistic Insights.Molecular neurobiology · 2025Review
- Role of miRNAs in Apoptosis Pathways of Immune Cells in Systemic Lupus Erythematosus.Immunity, inflammation and disease · 2025Review
- Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future Directions.Journal of nutrition and metabolism · 2025Review
- The Gut Microbiota Modulates Neuroinflammation in Alzheimer's Disease: Elucidating Crucial Factors and Mechanistic Underpinnings.CNS neuroscience & therapeutics · 2024Review
- Microbiome in urologic neoplasms: focusing on tumor immunity.Frontiers in immunology · 2024Review
- TRAF3 suppression encourages B cell recruitment and prolongs survival of microbiome-intact mice with ovarian cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Prognostic and Predictive Biomarkers in the Era of Immunotherapy for Lung Cancer.International journal of molecular sciences · 2023Review
- Fatty acid metabolism in adaptive immunity.The FEBS journal · 2023Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Class-switch DNA recombination (CSR) and somatic hypermutation (SHM), which require activation-induced cytidine deaminase (AID), and plasma cell differentiation, which requires B lymphocyte-induced maturation protein-1 (Blimp-1), are critical for the generation of class-switched and hypermutated (mature) Ab and autoantibody responses. We show that histone deacetylase inhibitors valproic acid and butyrate dampened AICDA/Aicda (AID) and PRDM1/Prdm1 (Blimp-1) mRNAs by upregulating miR-155, miR-181b, and miR-361 to silence AICDA/Aicda, and miR-23b, miR-30a, and miR-125b to silence PRDM1/Prdm1, in human and mouse B cells. This led to downregulation of AID, Blimp-1, and X-box binding protein 1, thereby inhibiting CSR, SHM, and plasma cell differentiation without altering B cell viability or proliferation. The selectivity of histone deacetylase inhibitor-mediated silencing of AICDA/Aicda and PRDM1/Prdm1 was emphasized by unchanged expression of HoxC4 and Irf4 (important inducers/modulators of AICDA/Aicda), Rev1 and Ung (central elements for CSR/SHM), and Bcl6, Bach2, or Pax5 (repressors of PRDM1/Prdm1 expression), as well as unchanged expression of miR-19a/b, miR-20a, and miR-25, which are not known to regulate AICDA/Aicda or PRDM1/Prdm1. Through these B cell-intrinsic epigenetic mechanisms, valproic acid blunted class-switched and hypermutated T-dependent and T-independent Ab responses in C57BL/6 mice. In addition, it decreased class-switched and hypermutated autoantibodies, ameliorated disease, and extended survival in lupus MRL/Fas(lpr/lpr) mice. Our findings outline epigenetic mechanisms that modulate expression of an enzyme (AID) and transcription factors (Blimp-1 and X-box binding protein 1) that are critical to the B cell differentiation processes that underpin Ab and autoantibody responses. They also provide therapeutic proof-of-principle in autoantibody-mediated autoimmunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.