ArticleThe Journal of experimental medicine2019
Active PI3K abrogates central tolerance in high-avidity autoreactive B cells.
Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- A viral glycoprotein targets IgGEMBO molecular medicine · 2026Article
- Immune Tolerance Regulation Is Critical to Immune Homeostasis.Journal of immunology research · 2025Review
- Regulation of Foxo1 expression is critical for central B cell tolerance and allelic exclusion.Cell reports · 2024Article
- CXCR4: from B-cell development to B cell-mediated diseases.Life science alliance · 2024Review
- Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model.Experimental and therapeutic medicine · 2023Article
- CD19 Is Internalized Together with IgM in Proportion to B Cell Receptor Stimulation and Is Modulated by Phosphatidylinositol 3-Kinase in Bone Marrow Immature B Cells.ImmunoHorizons · 2023Article
- LAPTM5 mediates immature B cell apoptosis and B cell tolerance by regulating the WWP2-PTEN-AKT pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Asymmetrical forward and reverse developmental trajectories determine molecular programs of B cell antigen receptor editing.Science immunology · 2022Article
- B-cell intrinsic and extrinsic signals that regulate central tolerance of mouse and human B cells.Immunological reviews · 2022Review
- P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance.The Journal of experimental medicine · 2022Article
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
- PI3K Isoforms in B Cells.Current topics in microbiology and immunology · 2022Article
- MicroRNA regulation of B cell receptor signaling.Immunological reviews · 2021Review
- The PI-3-Kinase P110α Catalytic Subunit of T Lymphocytes Modulates Collagen-Induced Arthritis.International journal of molecular sciences · 2021Article
- Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Activated PI3Kδ breaches multiple B cell tolerance checkpoints and causes autoantibody production.The Journal of experimental medicine · 2020Article
- Recent Advances in Lupus B Cell Biology: PI3K, IFNγ, and Chromatin.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Autoreactive B cells that bind self-antigen with high avidity in the bone marrow undergo mechanisms of central tolerance that prevent their entry into the peripheral B cell population. These mechanisms are breached in many autoimmune patients, increasing their risk of B cell-mediated autoimmune diseases. Resolving the molecular pathways that can break central B cell tolerance could therefore provide avenues to diminish autoimmunity. Here, we show that B cell-intrinsic expression of a constitutively active form of PI3K-P110α by high-avidity autoreactive B cells of mice completely abrogates central B cell tolerance and further promotes these cells to escape from the bone marrow, differentiate in peripheral tissue, and undergo activation in response to self-antigen. Upon stimulation with T cell help factors, these B cells secrete antibodies in vitro but remain unable to secrete autoantibodies in vivo. Overall, our data demonstrate that activation of the PI3K pathway leads high-avidity autoreactive B cells to breach central, but not late, stages of peripheral tolerance.
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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.