ArticleThe Journal of experimental medicine2015
Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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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
56 citing papers in PubMed, 73 citations in OpenAlex.
- FNIP1 Modulates B Cell Receptor Signaling Strength by Coordinating Metabolism During Development.bioRxiv : the preprint server for biology · 2026Article
- WAS Protein Deficiency Disrupts Memory B Cell Formation During Acute LCMV Infection.Journal of clinical immunology · 2026Article
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- Hypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.Journal of clinical immunology · 2025Article
- The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity.Brain : a journal of neurology · 2024Review
- Article
- Myelin oligodendrocyte glycoprotein antibody-associated disease as a novel presentation of central nervous system autoimmunity in a pediatric patient with Wiskott-Aldrich syndrome.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Article
- A novel statistical method for decontaminating T-cell receptor sequencing data.Briefings in bioinformatics · 2023Article
- Impacts of plasma microbial lipopolysaccharide translocation on B cell perturbations and anti-CD4 autoantibody production in people with HIV on suppressive antiretroviral therapy.Cell & bioscience · 2023Article
- The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART.NeuroImmune pharmacology and therapeutics · 2023Article
- COVID-19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity.Journal of medical virology · 2023Article
- HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions.Journal of clinical immunology · 2022Review
- Epigenetic regulation of B cells and its role in autoimmune pathogenesis.Cellular & molecular immunology · 2022Review
- Hem-1 regulates protective humoral immunity and limits autoantibody production in a B cell-specific manner.JCI insight · 2022Article
- B cells from anti-thyroid antibody positive, infertile women show hyper-reactivity to BCR stimulation.Frontiers in immunology · 2022Article
- NGS-Based B-Cell Receptor Repertoire AnalysisRepertoire analyses in the Context of Inborn Errors of Immunity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- ARPC1B binds WASP to control actin polymerization and curtail tonic signaling in B cells.JCI insight · 2021Article
- Autoantibodies in neurological disease.Nature reviews. Immunology · 2021Review
- Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies.Frontiers in immunology · 2021Article
- Autoimmunity in Wiskott-Aldrich Syndrome: Updated Perspectives.The application of clinical genetics · 2021Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder frequently associated with systemic autoimmunity, including autoantibody-mediated cytopenias. WAS protein (WASp)-deficient B cells have increased B cell receptor (BCR) and Toll-like receptor (TLR) signaling, suggesting that these pathways might impact establishment of the mature, naive BCR repertoire. To directly investigate this possibility, we evaluated naive B cell specificity and composition in WASp-deficient mice and WAS subjects (n = 12). High-throughput sequencing and single-cell cloning analysis of the BCR repertoire revealed altered heavy chain usage and enrichment for low-affinity self-reactive specificities in murine marginal zone and human naive B cells. Although negative selection mechanisms including deletion, anergy, and receptor editing were relatively unperturbed, WASp-deficient transitional B cells showed enhanced proliferation in vivo mediated by antigen- and Myd88-dependent signals. Finally, using both BCR sequencing and cell surface analysis with a monoclonal antibody recognizing an intrinsically autoreactive heavy chain, we show enrichment in self-reactive cells specifically at the transitional to naive mature B cell stage in WAS subjects. Our combined data support a model wherein modest alterations in B cell-intrinsic, BCR, and TLR signals in WAS, and likely other autoimmune disorders, are sufficient to alter B cell tolerance via positive selection of self-reactive transitional B cells.
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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.