ArticleJournal of immunology (Baltimore, Md. : 1950)2014
B cell-intrinsic TLR7 signaling is essential for the development of spontaneous germinal centers.
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 106 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.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Association of Toll-Like Receptor 7 (TLR7) Polymorphisms with Predisposition to Systemic Lupus Erythematosus (SLE): A Meta and Trial Sequential Analysis.Biochemical genetics · 2024Pooled it
- A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2019Trial
- IRF7 Protects Against Severe Influenza A Infection Independently of TLR7 Recognition in Mice.Viruses · 2026Article
- Evolution of self-reactive B cells: lessons from a lupus model.Biochemical Society transactions · 2026Review
- Article
- Serial intravital microscopy reveals temporal dynamics of autoreactive germinal centers in the spleen.iScience · 2026Article
- Plasmablast Storms: Microbial Drivers of Acute and Chronic Autoimmune Flares.Microorganisms · 2026Review
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- XIST expression and hypermethylation of the X chromosome in males with systemic lupus erythematosus.Frontiers in immunology · 2026Article
- CD21 primes extrafollicular differentiation of autoreactive B cells in a TLR7-driven lupus model.Science immunology · 2025Article
- Extrafollicular B Cell Responses-Is One Tent Big Enough?Immunological reviews · 2025Review
- Tlr9 expression protects against Tlr7-dependent exocrine gland and systemic disease manifestations in primary Sjögren's disease in a sex-biased manner.Journal of autoimmunity · 2025Article
- Sustained NPSLE-like phenotype in the absence of systemic lupus-like disease in TLR7-deficient B6.Nba2 mice.Brain, behavior, and immunity · 2025Article
- IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints.The Journal of experimental medicine · 2025Article
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- α-Ketoglutarate alleviates the pathogenesis of lupus and inhibits the activation and differentiation of B cells by promoting the expression of CD39.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- A TLR7 Agonist Conjugated to a Nanofibrous Peptide Hydrogel as a Potent Vaccine Adjuvant.Advanced healthcare materials · 2025Article
- Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- The path ahead for understanding Toll-like receptor-driven systemic autoimmunity.Current opinion in immunology · 2024Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Spontaneous germinal center (Spt-GC) B cells and follicular helper T cells generate high-affinity autoantibodies that are involved in the development of systemic lupus erythematosus. TLRs play a pivotal role in systemic lupus erythematosus pathogenesis. Although previous studies focused on the B cell-intrinsic role of TLR-MyD88 signaling on immune activation, autoantibody repertoire, and systemic inflammation, the mechanisms by which TLRs control the formation of Spt-GCs remain unclear. Using nonautoimmune C57BL/6 (B6) mice deficient in MyD88, TLR2, TLR3, TLR4, TLR7, or TLR9, we identified B cell-intrinsic TLR7 signaling as a prerequisite to Spt-GC formation without the confounding effects of autoimmune susceptibility genes and the overexpression of TLRs. TLR7 deficiency also rendered autoimmune B6.Sle1b mice unable to form Spt-GCs, leading to markedly decreased autoantibodies. Conversely, B6.yaa and B6.Sle1b.yaa mice expressing an extra copy of TLR7 and B6.Sle1b mice treated with a TLR7 agonist had increased Spt-GCs and follicular helper T cells. Further, TLR7/MyD88 deficiency led to compromised B cell proliferation and survival after B cell stimulation both in vitro and in vivo. In contrast, TLR9 inhibited Spt-GC development. Our findings demonstrate an absolute requirement for TLR7 and a negative regulatory function for TLR9 in Spt-GC formation under nonautoimmune and autoimmune conditions. Our data suggest that, under nonautoimmune conditions, Spt-GCs initiated by TLR7 produce protective Abs. However, in the presence of autoimmune susceptibility genes, TLR7-dependent Spt-GCs produce pathogenic autoantibodies. Thus, a single copy of TLR7 in B cells is the minimal requirement for breaking the GC-tolerance checkpoint.
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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.