Mature Human Bone Marrow Plasma Cells Secrete More IgG than Early-Minted Blood Antibody-Secreting Cells

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Abstract Plasma cells are known antibody-secreting factories with immunoglobulin (Ig) transcripts that increase as the cell matures into a long-lived plasma cell (LLPC) in the bone marrow (BM). Whether the Ig secretion rates among human antibody-secreting cells (ASC) are homogeneous or BM LLPC are capable of secreting more antibodies per cell compared to early-minted blood ASC remain unclear. Here, we use bulk and single cell cultures in a novel in vitro BM mimetic survival system to measure the IgG secretion rates of human ASC. We find that the mature BM ASC produce more IgG molecules per cell compared to immature, early-minted blood ASC. Furthermore, these blood ASC can mature into LLPC phenotypes in culture, and we show that ASC on day 7 secrete more IgG per cell than the input ASC from day 0. Thus, as human ASC mature, they increase the number of Ig transcripts and result in higher Ig secretion. These results also demonstrate that the mature ASC in the BM have higher Ig secretion rates compared to early-minted blood ASC.
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Mature Human Bone Marrow Plasma Cells Secrete More IgG than Early-Minted Blood Antibody-Secreting 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 Research Article Mature Human Bone Marrow Plasma Cells Secrete More IgG than Early-Minted Blood Antibody-Secreting Cells Doan C. Nguyen, Ian T. Hentenaar, Monica Cabrera-Mora, Shuya Kyu, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6585905/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 Plasma cells are known antibody-secreting factories with immunoglobulin (Ig) transcripts that increase as the cell matures into a long-lived plasma cell (LLPC) in the bone marrow (BM). Whether the Ig secretion rates among human antibody-secreting cells (ASC) are homogeneous or BM LLPC are capable of secreting more antibodies per cell compared to early-minted blood ASC remain unclear. Here, we use bulk and single cell cultures in a novel in vitro BM mimetic survival system to measure the IgG secretion rates of human ASC. We find that the mature BM ASC produce more IgG molecules per cell compared to immature, early-minted blood ASC. Furthermore, these blood ASC can mature into LLPC phenotypes in culture, and we show that ASC on day 7 secrete more IgG per cell than the input ASC from day 0. Thus, as human ASC mature, they increase the number of Ig transcripts and result in higher Ig secretion. These results also demonstrate that the mature ASC in the BM have higher Ig secretion rates compared to early-minted blood ASC. Immunology Full Text Additional Declarations The authors declare potential competing interests as follows: FEL is the founder of Micro-Bplex, Inc. and BeaconDx, Inc., serves on the scientific board of Be Biopharma, is a recipient of grants from the BMGF and Genentech, Inc., and has served as a consultant for Astra Zeneca. IS has consulted for GSK, Pfizer, Kayverna, Johnson & Johnson, Celgene, Bristol Myer Squibb, and Visterra. FEL, DCN, and IS are inventors of the patents concerning the plasma cell survival media related to this work (including US11124766B2, US11125757B2, US12163965B2, and US12173315B2). The other authors declare no conflicts of 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. 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. 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