{"paper_id":"1bc8d04d-fb4f-424f-811a-1cd800f270ab","body_text":"Discovery of a VLRB-GPIbβ-GPⅨ Complex Illuminates Lineage-Specific Redeployment of a Platelet Module for VLR Signaling | 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 Discovery of a VLRB-GPIbβ-GPⅨ Complex Illuminates Lineage-Specific Redeployment of a Platelet Module for VLR Signaling Shaochun Yuan, Lisi Deng, Xinli Wang, Zhiyuan Yang, Jiaqi Li, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8891980/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Unlike jawed vertebrates that rely on immunoglobulin (Ig)-based adaptive immunity, jawless vertebrates utilize variable lymphocyte receptors (VLRs) for antigen recognition. Despite extensive studies into VLR diversity and antigen recognition, the molecular mechanism coupling VLR engagement to lymphocyte activation remains unexplored. By mining single-cell and full-length transcriptomes data of lamprey and hagfish along with functional studies, we successfully discovered a VLRB cell-specific tripartite complex comprising VLRB, GPIbβ, and GPⅨ that transduces activation signals via an immunoreceptor tyrosine-based activation motif (ITAM) within GPIbβ. Phylogenetic reconstruction revealed that this complex originated from a lineage-specific duplication of the ancestral platelet GPIbα-GPIbβ-GPⅨ complex in agnathans, yielding two functionally divergent paralogs, one retained in thrombocytes and the other co-opted by VLRB lymphocytes. Transcriptional profiling further demonstrated that BHLHE41 and FOS serve as lineage-restricted co-regulators that coordinately govern expression of the VLRB-GPIbβ-GPⅨ subunits. Analogous to mammalian B cells, scRNA transcriptome revealed that VLRB cells can transition from a pre-activated to a post-activated state characterized by highly proliferative, plasma-like features, and concomitant up-regulation of the VLRB-GPIbβ-GPⅨ complex. Collectively, a lineage-specific gene-duplication event in agnathan repurposed a platelet-adhesion module into a VLRB cell-specific signaling complex through lineage-specific redeployment, unveiling a key missing link in VLR-mediated adaptive immunity. Biological sciences/Immunology/Adaptive immunity Biological sciences/Immunology/Immunogenetics jawless vertebrates ITAM scRNA-seq GPIb-Ⅸ VLRB complex Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementaryinformation.pdf Extened Data Figs and legends Cite Share Download PDF Status: Under Review 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8891980\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":592279060,\"identity\":\"4e42730f-3f14-4711-8919-d735fac000f1\",\"order_by\":0,\"name\":\"Shaochun 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