ArticleThe Journal of experimental medicine2010
Homeostatic expansion of autoreactive immunoglobulin-secreting cells in the Rag2 mouse model of Omenn syndrome.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 66 citations in OpenAlex.
- Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy.The Journal of clinical investigation · 2012Trial
- Trial
- IgE Production Beyond Classical T-Cell Help.Immune network · 2026Review
- Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.Science immunology · 2025Article
- Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Case report: Identification of a Chinese patient withFrontiers in immunology · 2024Article
- The recombinase activating genes: architects of immune diversity during lymphocyte development.Frontiers in immunology · 2023Review
- B cell abnormalities and autoantibody production in patients with partial RAG deficiency.Frontiers in immunology · 2023Review
- Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.Journal of clinical immunology · 2022Article
- Autoantibodies in immunodeficiency syndromes: The Janus faces of immune dysregulation.Blood reviews · 2022Review
- Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-betNature immunology · 2022Article
- RAG1 splicing mutation causes enhanced B cell differentiation and autoantibody production.JCI insight · 2021Article
- RAG deficiencies: Recent advances in disease pathogenesis and novel therapeutic approaches.European journal of immunology · 2021Review
- Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies.Frontiers in immunology · 2021Article
- Immune dysregulation in patients with RAG deficiency and other forms of combined immune deficiency.Blood · 2020Review
- Innovative Cell-Based Therapies and Conditioning to Cure RAG Deficiency.Frontiers in immunology · 2020Review
- Vasculitis as a Major Morbidity Factor in Patients With Partial RAG Deficiency.Frontiers in immunology · 2020Article
- Approaches to patients with variants in RAG genes: from diagnosis to timely treatment.Expert review of clinical immunology · 2019Review
- Recent advances in understanding RAG deficiencies.F1000Research · 2019Review
- RAG gene defects at the verge of immunodeficiency and immune dysregulation.Immunological reviews · 2019Review
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Authors and funding
18 authors at 9 institutions in 4 countries.
Funding
Abstract
Hypomorphic RAG mutations, leading to limited V(D)J rearrangements, cause Omenn syndrome (OS), a peculiar severe combined immunodeficiency associated with autoimmune-like manifestations. Whether B cells play a role in OS pathogenesis is so far unexplored. Here we report the detection of plasma cells in lymphoid organs of OS patients, in which circulating B cells are undetectable. Hypomorphic Rag2(R229Q) knock-in mice, which recapitulate OS, revealed, beyond severe B cell developmental arrest, a normal or even enlarged compartment of immunoglobulin-secreting cells (ISC). The size of this ISC compartment correlated with increased expression of Blimp1 and Xbp1, and these ISC were sustained by elevated levels of T cell derived homeostatic and effector cytokines. The detection of high affinity pathogenic autoantibodies toward target organs indicated defaults in B cell selection and tolerance induction. We hypothesize that impaired B cell receptor (BCR) editing and a serum B cell activating factor (BAFF) abundance might contribute toward the development of a pathogenic B cell repertoire in hypomorphic Rag2(R229Q) knock-in mice. BAFF-R blockade reduced serum levels of nucleic acid-specific autoantibodies and significantly ameliorated inflammatory tissue damage. These findings highlight a role for B cells in OS pathogenesis.
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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.