ArticleJournal of immunology (Baltimore, Md. : 1950)2013
TLR9 promotes tolerance by restricting survival of anergic anti-DNA B cells, yet is also required for their activation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
44 citing papers in PubMed, 60 citations in OpenAlex.
- Acute Sleep Deprivation and the Autoimmune TLR-BANK1 Pathway: Interplay with Gender and Emotional State.International journal of molecular sciences · 2025Article
- Deletion of Ptpn2 in B cells promotes autoimmunity via TLR and JAK/STAT signaling.JCI insight · 2025Article
- 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
- Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice.The Journal of experimental medicine · 2023Article
- Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus.Frontiers in immunology · 2023Review
- Genetic dissection of TLR9 reveals complex regulatory and cryptic proinflammatory roles in mouse lupus.Nature immunology · 2022Article
- B Cell Aberrance in Lupus: the Ringleader and the Solution.Clinical reviews in allergy & immunology · 2022Review
- Immunosenescence, aging and successful aging.Frontiers in immunology · 2022Review
- Insights Into the Host Contribution of Endocrine Associated Immune-Related Adverse Events to Immune Checkpoint Inhibition Therapy.Frontiers in oncology · 2022Review
- The Dynamics of B Cell Aging in Health and Disease.Frontiers in immunology · 2021Review
- B cell-intrinsic TLR9 expression is protective in murine lupus.The Journal of clinical investigation · 2020Article
- Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells.Nature immunology · 2019Article
- Nur77 Links Chronic Antigen Stimulation to B Cell Tolerance by Restricting the Survival of Self-Reactive B Cells in the Periphery.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Protective Role of Myeloid Cells Expressing a G-CSF Receptor Polymorphism in an Induced Model of Lupus.Frontiers in immunology · 2018Article
- New application of anti-TLR monoclonal antibodies: detection, inhibition and protection.Inflammation and regeneration · 2018Review
- Mouse models of lupus: what they tell us and what they don't.Lupus science & medicine · 2018Article
- Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)-5 and TLR-9 in lupus nephritis.Clinical and experimental immunology · 2017Article
- Altered B cell signalling in autoimmunity.Nature reviews. Immunology · 2017Review
- Mechanisms of central tolerance for B cells.Nature reviews. Immunology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Nucleic acid-reactive B cells frequently arise in the bone marrow but are tolerized by mechanisms including receptor editing, functional anergy, and/or deletion. TLR9, a sensor of endosomal dsDNA, both promotes and regulates systemic autoimmunity in vivo, but the precise nature of its apparently contradictory roles in autoimmunity remained unclear. In this study, using the 3H9 anti-DNA BCR transgene in the autoimmune-prone MRL.Fas(lpr) mouse model of systemic lupus erythematosus, we identify the stages at which TLR9 contributes to establishing and breaking B cell tolerance. Although TLR9 is dispensable for L chain editing during B cell development in the bone marrow, TLR9 limits anti-DNA B cell life span in the periphery and is thus tolerogenic. In the absence of TLR9, anti-DNA B cells have much longer life spans and accumulate in the follicle, neither activated nor deleted. These cells retain some characteristics of anergic cells, in that they have elevated basal BCR signaling but impaired induced responses and downregulate their cell-surface BCR expression. In contrast, whereas TLR9-intact anergic B cells accumulate near the T/B border, TLR9-deficient anti-DNA B cells are somewhat more dispersed throughout the follicle. Nonetheless, in older autoimmune-prone animals, TLR9 expression specifically within the B cell compartment is required for spontaneous peripheral activation of anti-DNA B cells and their differentiation into Ab-forming cells via an extrafollicular pathway. Thus, TLR9 has paradoxical roles in regulating anti-DNA B cells: it helps purge the peripheral repertoire of autoreactive cells, yet is also required for their activation.
Indexed as
Identifiers
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.