ArticleNature immunology2019
The AKT kinase signaling network is rewired by PTEN to control proximal BCR signaling in germinal center B cells.
Article in Nature immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
- The B-cell Receptor Blueprint in Lymphoma: Mechanisms and Therapeutic Opportunities.Blood cancer discovery · 2026Review
- Virus-like antigen display delivers a stand-alone danger signal through the BCR that circumvents tolerance.bioRxiv : the preprint server for biology · 2026Article
- Lymphocyte-derived cholinergic circuits modulate germinal center output and B cell activation.Nature immunology · 2026Article
- Urolithin A blocks colorectal cancer progression by AKT1 inhibition-driven immune activation.Scientific reports · 2026Article
- PTEN-mTORC2 signaling module controls antibody isotype selection and antiviral humoral immunity.Frontiers in immunology · 2026Article
- MIZ-1 controls transcriptional programs required for BCR signaling, actin dynamics, and naïve B cell survival.Frontiers in immunology · 2026Article
- PTEN restricts IL-21R signaling in GC B cells and suppresses their differentiation to plasma cells.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- 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
- Emerging novel methodologies to understand and strategically target long-lived plasma cells in vaccine design to induce durable immunity.Frontiers in immunology · 2025Review
- Physical extraction of antigen and information.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TFEB activation hallmarks antigenic experience of B lymphocytes and directs germinal center fate decisions.Nature communications · 2024Article
- Csk restrains BCR-mediated ROS production and contributes to germinal center selection and affinity maturation.The Journal of experimental medicine · 2024Article
- Accelerated plasma-cell differentiation in Bach2-deficient mouse B cells is caused by altered IRF4 functions.The EMBO journal · 2024Article
- Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation.Immunity · 2024Article
- Phosphatidylserine synthesis controls oncogenic B cell receptor signaling in B cell lymphoma.The Journal of cell biology · 2024Article
- B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection.Immunity · 2023Article
- Combination CTLA4Ig and Anti-CD40 Ligand Treatment Modifies T and B Cell Metabolic Profiles and Promotes B Cell Receptor Remodeling in a Mouse Model of Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells.Science immunology · 2023Article
- SREBP signaling is essential for effective B cell responses.Nature immunology · 2023Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
B cell antigen receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to optimize selection for high-affinity B cells. In GCBC, BCR signals are constrained, but the mechanisms are not well understood. Here we describe a GC-specific, AKT-kinase-driven negative feedback loop that attenuates BCR signaling. Mass spectrometry revealed that AKT target activity was altered in GCBCs compared with naive B cells. Retargeting was linked to differential AKT T308 and S473 phosphorylation, in turn controlled by GC-specific upregulation of phosphoinositide-dependent protein kinase PDK1 and the phosphatase PTEN. In GCBCs, AKT preferentially targeted CSK, SHP-1 and HPK1, which are negative regulators of BCR signaling. We found that phosphorylation enhances enzymatic activity of these proteins, creating a negative feedback loop that dampens upstream BCR signaling. AKT inhibition relieved this negative feedback and enhanced activation of BCR-proximal kinase LYN, as well as downstream BCR signaling molecules in GCBCs.
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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.