ArticleThe Journal of allergy and clinical immunology2014
Signaling lymphocytic activation molecule (SLAM)/SLAM-associated protein pathway regulates human B-cell tolerance.
Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Multiomic Signatures of Chronic Beryllium Disease Bronchoalveolar Lavage Cells Relate to T-Cell Function and Innate Immunity.American journal of respiratory cell and molecular biology · 2022Article
- Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen-Specific Clones.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Activation induced cytidine deaminase: An old friend with new faces.Frontiers in immunology · 2022Review
- SLAM Associated Protein Signaling in T Cells: Tilting the Balance Toward Autoimmunity.Frontiers in immunology · 2021Review
- Autoantibody Profiling in Plasma of Dengue Virus-Infected Individuals.Pathogens (Basel, Switzerland) · 2020Article
- Homeostasis and regulation of autoreactive B cells.Cellular & molecular immunology · 2020Review
- Early B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production.Brain : a journal of neurology · 2019Article
- AIRE expression controls the peripheral selection of autoreactive B cells.Science immunology · 2019Observational
- The novel immunoglobulin super family receptor SLAMF9 identified in TAM of murine and human melanoma influences pro-inflammatory cytokine secretion and migration.Cell death & disease · 2018Article
- X-Linked Lymphoproliferative Disease Type 1: A Clinical and Molecular Perspective.Frontiers in immunology · 2018Review
- Decreased somatic hypermutation induces an impaired peripheral B cell tolerance checkpoint.The Journal of clinical investigation · 2016Article
- Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Compromised fidelity of B-cell tolerance checkpoints in AChR and MuSK myasthenia gravis.Annals of clinical and translational neurology · 2016Article
- Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance.Immunity · 2015Article
- Immunogenetics of autoimmune thyroid diseases: A comprehensive review.Journal of autoimmunity · 2015Review
- Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients.The Journal of clinical investigation · 2015Article
- The ups and downs of negative (and positive) selection of B cells.The Journal of clinical investigation · 2015Article
- B lymphocytes in neuromyelitis optica.Neurology(R) neuroimmunology & neuroinflammation · 2015Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundSignaling lymphocytic activation molecule (SLAM)-associated protein (SAP) can mediate the function of SLAM molecules, which have been proposed to be involved in the development of autoimmunity in mice.
objectiveWe sought to determine whether the SLAM/SAP pathway regulates the establishment of human B-cell tolerance and what mechanisms of B-cell tolerance could be affected by SAP deficiency.
methodsWe tested the reactivity of antibodies isolated from single B cells from SAP-deficient patients with X-linked lymphoproliferative disease (XLP). The expressions of SAP and SLAM family members were assessed in human bone marrow-developing B cells. We also analyzed regulatory T (Treg) cell function in patients with XLP and healthy control subjects.
resultsWe found that new emigrant/transitional B cells from patients with XLP were enriched in autoreactive clones, revealing a defective central B-cell tolerance checkpoint in the absence of functional SAP. In agreement with a B cell-intrinsic regulation of central tolerance, we identified SAP expression in a discrete subset of bone marrow immature B cells. SAP colocalized with SLAMF6 only in association with clustered B-cell receptors likely recognizing self-antigens, suggesting that SLAM/SAP regulate B-cell receptor-mediated central tolerance. In addition, patients with XLP displayed defective peripheral B-cell tolerance, which is normally controlled by Treg cells. Treg cells in patients with XLP seem functional, but SAP-deficient T cells were resistant to Treg cell-mediated suppression. Indeed, SAP-deficient T cells were hyperresponsive to T-cell receptor stimulation, which resulted in increased secretion of IL-2, IFN-γ, and TNF-α.
conclusionsSAP expression is required for the counterselection of developing autoreactive B cells and prevents their T cell-dependent accumulation in the periphery.
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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.