ArticleImmunity2008
IRAK-4- and MyD88-dependent pathways are essential for the removal of developing autoreactive B cells in humans.
Article in Immunity, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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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
124 citing papers in PubMed, 212 citations in OpenAlex.
- IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens.Blood · 2014Trial
- Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy.The Journal of clinical investigation · 2012Trial
- Failure of early B cell tolerance and possible BCR signaling dysregulation underlie NF155-mediated autoimmune nodopathies.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- Genetic Convergence Analysis of CRISPR Perturbations Deciphers Gene Functional Similarity.bioRxiv : the preprint server for biology · 2025Article
- Human genetic influences on early B cell development.Journal of human immunity · 2025Review
- Article
- Signaling pathways in systemic lupus erythematosus and therapeutic implications.Frontiers in immunology · 2025Review
- 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
- Epigenetic regulation of B cells and its role in autoimmune pathogenesis.Cellular & molecular immunology · 2022Review
- Review
- B-cell intrinsic and extrinsic signals that regulate central tolerance of mouse and human B cells.Immunological reviews · 2022Review
- Positive and negative selection shape the human naive B cell repertoire.The Journal of clinical investigation · 2022Article
- Activation induced cytidine deaminase: An old friend with new faces.Frontiers in immunology · 2022Review
- The m6A methylation profiles of immune cells in type 1 diabetes mellitus.Frontiers in immunology · 2022Article
- Immunogenetics of Lupus Erythematosus.Advances in experimental medicine and biology · 2022Article
- 1,4-Naphthoquinone Is a Potent Inhibitor of IRAK1 Kinases and the Production of Inflammatory Cytokines in THP-1 Differentiated Macrophages.ACS omega · 2021Article
- Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?Biomolecules · 2021Review
- Identification ofPathogens (Basel, Switzerland) · 2021Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 5 countries.
Funding
Abstract
Most autoreactive B cells are normally counterselected during early B cell development. To determine whether Toll-like receptors (TLRs) regulate the removal of autoreactive B lymphocytes, we tested the reactivity of recombinant antibodies from single B cells isolated from patients deficient for interleukin-1 receptor-associated kinase 4 (IRAK-4), myeloid differentiation factor 88 (MyD88), and UNC-93B. Indeed, all TLRs except TLR3 require IRAK-4 and MyD88 to signal, and UNC-93B-deficient cells are unresponsive to TLR3, TLR7, TLR8, and TLR9. All patients suffered from defective central and peripheral B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive mature naive B cells in their blood. Hence, TLR7, TLR8, and TLR9 may prevent the recruitment of developing autoreactive B cells in healthy donors. Paradoxically, IRAK-4-, MyD88-, and UNC-93B-deficient patients did not display autoreactive antibodies in their serum or develop autoimmune diseases, suggesting that IRAK-4, MyD88, and UNC-93B pathway blockade may thwart autoimmunity in humans.
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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.