ArticleThe Journal of clinical investigation2022
Immune dysregulation caused by homozygous mutations in CBLB.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 38 citations in OpenAlex.
- [Ubiquitination-mediated regulation of T cell homeostasis and autoimmune diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Interleukin-2 transcriptomic expression correlates with prolonged survival and with GNAS alterations in patients with advanced cancers.ESMO open · 2026Article
- Mesenchymal stem cell-derived exosomal CBLB ameliorates infantile pneumonia progression probably by ubiquitinating MAPK14.Journal of inflammation (London, England) · 2025Article
- Rescuing natural killer cells from the cancer wilderness.Journal for immunotherapy of cancer · 2025Article
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- Update on type 2 immunity.The Journal of allergy and clinical immunology · 2025Review
- Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions.Life (Basel, Switzerland) · 2024Review
- Exploring the role of CBLB in acute myocardial infarction: transcriptomic, microbiomic, and metabolomic analyses.Journal of translational medicine · 2024Article
- IKZF1 and UBR4 gene variants drive autoimmunity and Th2 polarization in IgG4-related disease.The Journal of clinical investigation · 2024Article
- ISG15/GRAIL1/CD3 axis influences survival of patients with esophageal adenocarcinoma.JCI insight · 2024Article
- The immunobiology of myelodysplastic neoplasms: a mini-review.Frontiers in immunology · 2024Review
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Construction of a T cell receptor signaling range for spontaneous development of autoimmune disease.The Journal of experimental medicine · 2023Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 4 countries.
Funding
Abstract
CBL-B is an E3 ubiquitin ligase that ubiquitinates proteins downstream of immune receptors to downregulate positive signaling cascades. Distinct homozygous mutations in CBLB were identified in 3 unrelated children with early-onset autoimmunity, one of whom also had chronic urticaria. Patient T cells exhibited hyperproliferation in response to anti-CD3 cross-linking. One of the mutations, p.R496X, abolished CBL-B expression, and a second mutation, p.C464W, resulted in preserved CBL-B expression. The third mutation, p.H285L in the SH2 domain of CBL-B, was expressed at half the normal level in the patient's cells. Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient's p.H285L mutation, had T and B cell hyperproliferation in response to antigen receptor cross-linking. CblbH257L mice had increased percentages of T regulatory cells (Tregs) that had normal in vitro suppressive function. However, T effector cells from the patient with the p.H285L mutation and CblbH257L mice were resistant to suppression by WT Tregs. Bone marrow-derived mast cells from CblbH257L mice were hyperactivated after FcεRI cross-linking, and CblbH257L mice demonstrated exaggerated IgE-mediated passive anaphylaxis. This study establishes CBL-B deficiency as a cause of immune dysregulation.
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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.