Purine Synthesis Pathways Activate mTORC1 in B cells

Purine Synthesis Pathways Activate mTORC1 in B cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Purine Synthesis Pathways Activate mTORC1 in B cells Rohit Antony, Diondre Reyes, Peter Kim, Macaul Crici, Gabrielle Elliott, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7879378/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The mechanistic target of rapamycin complex 1 (mTORC1) regulates cellular metabolism by sensing growth factors and nutrient availability to support growth and division. In quiescent B cells, mTORC1 activity is low, but it rapidly increases upon engagement of activating receptors, such as antigen receptors, co-receptors, and Toll-like receptors. The magnitude of mTORC1 activity fine-tunes both the proliferative capacity and protein synthesis potential of activated B cells, broadly influencing humoral immunity. Elevated mTORC1 activity has been reported in lymphocytes from patients with autoimmune diseases, and pharmacological inhibition of mTORC1 reduces antibody titers. We and others have previously shown that the E3 ubiquitin ligase Itch negatively modulates mTORC1 activity in B cells and regulates antibody levels in humans and mice. Here, we investigate how Itch regulates mTORC1 activity following TLR9 engagement in B cells. Our results show an unexpected role for Itch in limiting purine synthesis-dependent mTORC1 activation in B cells. Purine sensing represents a novel target for fine control of mTORC1 activity in B cells, with therapeutic potential for diseases where mTORC1 hyperactivation contributes to pathogenesis. Biological sciences/Immunology/Lymphocytes/B cells/B-2 cells Biological sciences/Immunology/Adaptive immunity/Cellular immunity/Lymphocyte activation Biological sciences/Molecular biology/Post-translational modifications/Ubiquitylation Biological sciences/Cell biology/Cell growth/TOR signalling Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7879378","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":532494412,"identity":"bd944ac8-3ad0-40be-a523-5b36f3d0e0cd","order_by":0,"name":"Rohit Antony","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Rohit","middleName":"","lastName":"Antony","suffix":""},{"id":532494413,"identity":"5b35c795-6f96-4c2a-a175-ed30df3e02bb","order_by":1,"name":"Diondre 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