ArticleThe Journal of clinical investigation2017
A TLR9-dependent checkpoint governs B cell responses to DNA-containing antigens.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis.Frontiers in genetics · 2023Pooled it
- Circulating and intrahepatic antiviral B cells are defective in hepatitis B.The Journal of clinical investigation · 2018Trial
- The Developmental and Functional Implications of Age-Associated B Cells (ABCs) Across Tissue Microenvironments.Immunological reviews · 2026Review
- Clotting the Gap Between Mitochondria-Mediated Immunity and Mitochondrial Transfer.Circulation research · 2026Review
- Lyn governs the establishment and maintenance of B cell anergy by suppressing PI3K signaling.Nature communications · 2026Article
- X-linked transcriptome dysregulation across immune cells in systemic lupus erythematosus.Biology of sex differences · 2025Article
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- Coordinated Regulation of Extrafollicular B Cell Responses by IL-12 and IFNγ.Immunological reviews · 2025Review
- Nucleic acid triggers of autoimmunity and autoinflammation.Current opinion in immunology · 2025Review
- Article
- A TNIP1-driven systemic autoimmune disorder with elevated IgG4.Nature immunology · 2024Article
- Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis.Nature communications · 2024Article
- Failed Downregulation of PI3K Signaling Makes Autoreactive B Cells Receptive to Bystander T Cell Help.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10Frontiers in immunology · 2024Article
- TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance.The Journal of experimental medicine · 2023Article
- Disease in the Pld4thss/thss Model of Murine Lupus Requires TLR9.ImmunoHorizons · 2023Article
- Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- TLR9 Signaling Is Required for theInternational journal of molecular sciences · 2023Article
- Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus.Frontiers in immunology · 2023Review
- Single-cell profiling of CD11c+ B cells in atherosclerosis.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells. Survival or costimulatory signals rescue B cells from this fate, but the outcome varies depending on the signals involved. B lymphocyte stimulator (BLyS) engenders survival and antibody secretion, whereas CD40 costimulation with IL-21 or IFN-γ promotes a T-bet+ B cell phenotype. Finally, in vivo immunization studies revealed that when protein antigens are conjugated with DNA, the humoral immune response is blunted and acquires features associated with T-bet+ B cell differentiation. We propose that this mechanism integrating BCR, TLR9, and cytokine signals provides a peripheral checkpoint for DNA-containing antigens that, if circumvented by survival and differentiative cues, yields B cells with the autoimmune-associated T-bet+ phenotype.
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What OpenQuestion holds
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.