ArticleJournal of immunology (Baltimore, Md. : 1950)2007
Basal B cell receptor-directed phosphatidylinositol 3-kinase signaling turns off RAGs and promotes B cell-positive selection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 98 citations in OpenAlex.
- Viral subversion of B-cell tolerance: mechanisms linking infection to autoimmunity.EMBO reports · 2026Review
- From PGT-M discovery to mechanism: functional validation of novel compound heterozygous RAG1 mutations in severe combined immunodeficiency.Journal of assisted reproduction and genetics · 2026Article
- ImmunoMatch learns and predicts cognate pairing of heavy and light immunoglobulin chains.Nature methods · 2026Article
- Regulation of Foxo1 expression is critical for central B cell tolerance and allelic exclusion.Cell reports · 2024Article
- 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
- 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
- The recombinase activating genes: architects of immune diversity during lymphocyte development.Frontiers in immunology · 2023Review
- 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
- PI3K Isoforms in B Cells.Current topics in microbiology and immunology · 2022Article
- MicroRNA regulation of B cell receptor signaling.Immunological reviews · 2021Review
- 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
- Regulatory Non-Coding RNAs Modulate Transcriptional Activation During B Cell Development.Frontiers in genetics · 2021Review
- Recent Advances in Lupus B Cell Biology: PI3K, IFNγ, and Chromatin.Frontiers in immunology · 2020Review
- Cross-Reactive Antigen Expressed by B6 Splenocytes Drives Receptor Editing and Marginal Zone Differentiation of IgG2a-Reactive AM14 Vκ8 B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Active PI3K abrogates central tolerance in high-avidity autoreactive B cells.The Journal of experimental medicine · 2019Article
- Differences in Self-Recognition between Secreted Antibody and Membrane-Bound B Cell Antigen Receptor.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Antibody repertoire analysis in polygenic autoimmune diseases.Immunology · 2018Review
- Foxo3 Promotes Apoptosis of B Cell Receptor-Stimulated Immature B Cells, Thus Limiting the Window for Receptor Editing.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
PI3K plays key roles in cell growth, differentiation, and survival by generating the second messenger phosphatidylinositol-(3,4,5)-trisphosphate (PIP3). PIP3 activates numerous enzymes, in part by recruiting them from the cytosol to the plasma membrane. We find that in immature B lymphocytes carrying a nonautoreactive Ag receptor, PI3K signaling suppresses RAG expression and promotes developmental progression. Inhibitors of PI3K signaling abrogate this positive selection. Furthermore, immature primary B cells from mice lacking the p85alpha regulatory subunit of PI3K suppress poorly RAG expression, undergo an exaggerated receptor editing response, and, as in BCR-ligated cells, fail to progress into the G1 phase of cell cycle. Moreover, immature B cells carrying an innocuous receptor have sustained elevation of PIP3 levels and activation of the downstream effectors phospholipase C (PLC)gamma2, Akt, and Bruton's tyrosine kinase. Of these, PLCgamma2 appears to play the most significant role in down-regulating RAG expression. It therefore appears that when the BCR of an immature B cell is ligated, PIP3 levels are reduced, PLCgamma2 activation is diminished, and receptor editing is promoted by sustained RAG expression. Taken together, our results provide evidence that PI3K signaling is an important cue required for fostering development of B cells carrying a useful BCR.
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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.