ArticleThe Journal of experimental medicine2013
The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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
52 citing papers in PubMed, 87 citations in OpenAlex.
- Article
- Targeted intestinal barrier repairActa pharmaceutica Sinica. B · 2026Article
- Review
- Structural insights into human signal peptide peptidase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrated analysis of COVID-19 multi-omics data for eQTLs reveals genetic mechanisms underlying disease severity.bioRxiv : the preprint server for biology · 2025Article
- WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD.International journal of molecular sciences · 2024Review
- Genome-Wide Identification of the SPP/SPPL Gene Family andInternational journal of molecular sciences · 2024Article
- Dynamic association of the intramembrane proteases SPPL2a/b and their substrates with tetraspanin-enriched microdomains.iScience · 2023Article
- Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis.Nature communications · 2022Article
- Interplay between soluble CD74 and macrophage-migration inhibitory factor drives tumor growth and influences patient survival in melanoma.Cell death & disease · 2022Article
- Physiological functions of SPP/SPPL intramembrane proteases.Cellular and molecular life sciences : CMLS · 2020Review
- Impaired proteolysis by SPPL2a causes CD74 fragment accumulation that can be recognized by anti-CD74 autoantibodies in human ankylosing spondylitis.European journal of immunology · 2020Article
- Mendelian susceptibility to mycobacterial disease: recent discoveries.Human genetics · 2020Review
- Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis.Communications biology · 2020Article
- Signaling Functions of Intramembrane Aspartyl-Proteases.Frontiers in cardiovascular medicine · 2020Review
- The immunobiology of MIF: function, genetics and prospects for precision medicine.Nature reviews. Rheumatology · 2019Review
- Discovery of Orally Active Hydroxyethylamine Based SPPL2a Inhibitors.ACS medicinal chemistry letters · 2019Article
- Measurement of CD74 N-terminal Fragment Accumulation in Cells Treated with SPPL2a Inhibitor.Bio-protocol · 2019Article
- Mendelian susceptibility to mycobacterial disease: 2014-2018 update.Immunology and cell biology · 2019Review
- Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis.The Journal of experimental medicine · 2019Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
B cell development requires tight regulation to allow for the generation of a diverse repertoire while preventing the development of autoreactive cells. We report, using N-ethyl-N-nitrosourea (ENU)-induced mutagenesis, the identification of a mutant mouse (chompB) with a block in early B cell development. The blockade occurs after the transitional 1 (T1) stage and leads to a decrease in mature B cell subsets and deficits in T cell-dependent antibody responses. Additionally, chompB mice have decreases in myeloid dendritic cells (DCs). The mutation was mapped to the intramembrane protease signal peptide peptidase-like 2a (Sppl2a), a gene not previously implicated in immune cell development. Proteomic analysis identified the invariant chain (CD74) as a key substrate of Sppl2a and suggests that regulated intramembrane proteolysis of CD74 by Sppl2a contributes to B cell and DC survival. Moreover, these data suggest that modulation of Sppl2a may be a useful therapeutic strategy for treatment of B cell dependent autoimmune disorders.
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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.