ArticleMolecular cell2010
AID-induced genotoxic stress promotes B cell differentiation in the germinal center via ATM and LKB1 signaling.
Article in Molecular cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 87 citations in OpenAlex.
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- Current Insights into Glutathione Depletion in Adult Septic Patients.Antioxidants (Basel, Switzerland) · 2025Review
- Knockdown of USF1 and USF2 drives prolonged changes in the gene expression response of M12-5B3 cells to DNA damage.PloS one · 2025Article
- Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress.Developmental cell · 2024Article
- Cell Reprogramming and Differentiation Utilizing Messenger RNA for Regenerative Medicine.Journal of developmental biology · 2023Review
- Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis.Current issues in molecular biology · 2023Review
- Mechanism and regulation of secondary immunoglobulin diversification.Cell cycle (Georgetown, Tex.) · 2023Review
- Metabolic changes induced by DNA damage in Ramos cells: exploring the role of mTORC1 complex.FEBS open bio · 2022Article
- Review
- The Determinants of B Cell Receptor Signaling as Prototype Molecular Biomarkers of Leukemia.Frontiers in oncology · 2021Article
- Tertiary lymphoid structure related B-cell IgE isotype switching and secondary lymphoid organ linked IgE production in mouse allergy model.BMC immunology · 2020Article
- An immune-centric exploration of BRCA1 and BRCA2 germline mutation related breast and ovarian cancers.BMC cancer · 2020Article
- Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse.Frontiers in immunology · 2020Review
- A Protein Antagonist of Activation-Induced Cytidine Deaminase Encoded by a Complex Mouse Retrovirus.mBio · 2019Article
- Ampk regulates IgD expression but not energy stress with B cell activation.Scientific reports · 2019Article
- At the intersection of DNA damage and immune responses.Nature reviews. Immunology · 2019Review
- Adaptive Transcriptional Responses by CRTC Coactivators in Cancer.Trends in cancer · 2019Review
- Immune response to influenza vaccination in the elderly is altered by chronic medication use.Immunity & ageing : I & A · 2018Article
- The Effect of Resveratrol on Cell Viability in the Burkitt's Lymphoma Cell Line Ramos.Molecules (Basel, Switzerland) · 2017Article
- Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells.Nature communications · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
During an immune response, B cells undergo rapid proliferation and activation-induced cytidine deaminase (AID)-dependent remodeling of immunoglobulin (IG) genes within germinal centers (GCs) to generate memory B and plasma cells. Unfortunately, the genotoxic stress associated with the GC reaction also promotes most B cell malignancies. Here, we report that exogenous and intrinsic AID-induced DNA strand breaks activate ATM, which signals through an LKB1 intermediate to inactivate CRTC2, a transcriptional coactivator of CREB. Using genome-wide location analysis, we determined that CRTC2 inactivation unexpectedly represses a genetic program that controls GC B cell proliferation, self-renewal, and differentiation while opposing lymphomagenesis. Inhibition of this pathway results in increased GC B cell proliferation, reduced antibody secretion, and impaired terminal differentiation. Multiple distinct pathway disruptions were also identified in human GC B cell lymphoma patient samples. Combined, our data show that CRTC2 inactivation, via physiologic DNA damage response signaling, promotes B cell differentiation in response to genotoxic stress.
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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.