ArticleProceedings of the National Academy of Sciences of the United States of America2014
mTOR kinase inhibitors promote antibody class switching via mTORC2 inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Immunoregulation with mTOR inhibitors to prevent COVID-19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines.Journal of medical virology · 2020Pooled it
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- Strategies for Evading Cellular Immunity Against Recombinant AAV Vectors in Gene Therapy.Current medical science · 2026Review
- PTEN-mTORC2 signaling module controls antibody isotype selection and antiviral humoral immunity.Frontiers in immunology · 2026Article
- Targeting mTOR in Systemic Lupus Erythematosus: From Immune Cell Dysfunction to Clinical Translation.Journal of inflammation research · 2026Review
- Reporter immunogenicity as a defined rejection antigen: a noninvasive platform for skin transplant immunobiology.Frontiers in immunology · 2026Article
- SIV-specific neutralizing antibody induction following selection of a PI3K drive-attenuatedeLife · 2025Article
- Signaling Activation and Modulation in Extrafollicular B Cell Responses.Immunological reviews · 2025Review
- Viral-mediated gene therapy in pediatric neurological disorders.World journal of pediatrics : WJP · 2024Review
- Use of plasmapheresis to lower anti-AAV antibodies in nonhuman primates with pre-existing immunity to AAVrh74.Molecular therapy. Methods & clinical development · 2024Article
- Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases.Biomedicines · 2023Review
- B cell activation via immunometabolism in systemic lupus erythematosus.Frontiers in immunology · 2023Review
- Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.Molecular therapy. Methods & clinical development · 2022Review
- Metabolic changes induced by DNA damage in Ramos cells: exploring the role of mTORC1 complex.FEBS open bio · 2022Article
- miR-582 negatively regulates pre-B cell proliferation and survival through targeting Hif1α and Rictor.Cell death & disease · 2022Article
- A versatile toolkit for overcoming AAV immunity.Frontiers in immunology · 2022Review
- Article
- Immunomodulation in Administration of rAAV: Preclinical and Clinical Adjuvant Pharmacotherapies.Frontiers in immunology · 2021Review
- Mechanisms of Dysregulated Humoral and Cellular Immunity by SARS-CoV-2.Pathogens (Basel, Switzerland) · 2020Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The mammalian target of rapamycin (mTOR) is a kinase that functions in two distinct complexes, mTORC1 and mTORC2. In peripheral B cells, complete deletion of mTOR suppresses germinal center B-cell responses, including class switching and somatic hypermutation. The allosteric mTORC1 inhibitor rapamycin blocks proliferation and differentiation, but lower doses can promote protective IgM responses. To elucidate the complexity of mTOR signaling in B cells further, we used ATP-competitive mTOR kinase inhibitors (TOR-KIs), which inhibit both mTORC1 and mTORC2. Although TOR-KIs are in clinical development for cancer, their effects on mature lymphocytes are largely unknown. We show that high concentrations of TOR-KIs suppress B-cell proliferation and differentiation, yet lower concentrations that preserve proliferation increase the fraction of B cells undergoing class switching in vitro. Transient treatment of mice with the TOR-KI compound AZD8055 increased titers of class-switched high-affinity antibodies to a hapten-protein conjugate. Mechanistic investigation identified opposing roles for mTORC1 and mTORC2 in B-cell differentiation and showed that TOR-KIs enhance class switching in a manner dependent on forkhead box, subgroup O (FoxO) transcription factors. These observations emphasize the distinct actions of TOR-KIs compared with rapamycin and suggest that TOR-KIs might be useful to enhance production of class-switched antibodies following vaccination.
Indexed as
Identifiers
What OpenQuestion holds
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.