{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:27:20Z","timestamp":1792459640355,"version":"4.5.0"},"posted":{"date-parts":[[2026,5,7]]},"group-title":"Developmental Biology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["P51 OD011132"],"award-info":[{"award-number":["P51 OD011132"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S10 OD026799"],"award-info":[{"award-number":["S10 OD026799"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AI099108"],"award-info":[{"award-number":["R01AI099108"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30CA023074"],"award-info":[{"award-number":["P30CA023074"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AI182276"],"award-info":[{"award-number":["R01AI182276"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FDN159937"],"award-info":[{"award-number":["FDN159937"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-051356"],"award-info":[{"award-number":["INV-051356"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-071091"],"award-info":[{"award-number":["INV-071091"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-007910"],"award-info":[{"award-number":["INV-007910"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-044064"],"award-info":[{"award-number":["INV-044064"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-071644"],"award-info":[{"award-number":["INV-071644"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-050917"],"award-info":[{"award-number":["INV-050917"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>The ability to generate functional B cells from human pluripotent stem cells (hPSCs) would open new opportunities to develop novel B cell-based therapies to treat a range of human diseases and disorders. Towards this goal, we established a protocol that promotes the efficient development of B lineage cells from definitive hematopoietic progenitors generated from different hPSC lines. Flow cytometric and multi-omic scRNA-seq analyses revealed that B cell development from hPSCs transitions through the well-established pro-B, pre-B and na\u00efve B cell stages, accurately recapitulating B lymphopoiesis in the human adult bone marrow. Importantly, the na\u00efve B cells generated with this approach could be induced to mature into plasma cells that secrete antibodies and undergo class switching. Analyses of signaling pathways that regulate B lymphopoiesis in these cultures uncovered a potent inhibitory effect of IL-7 on functional IgH rearrangement, resulting in the development of abnormal cells that failed to undergo pre-B cell maturation. Finally, analysis of the different hPSC-derived hematopoietic programs revealed that both definitive and yolk sac progenitors display B cell potential, indicating that there are distinct developmental sources of human B lineage cells. Taken together, these findings demonstrate the efficient generation of B cells from hPSCs and, in doing so, provide a system for further investigating the earliest stages of human B lymphopoiesis and a source of appropriately staged plasma cells for future therapeutic applications.<\/jats:p>","DOI":"10.64898\/2026.05.04.722674","type":"posted-content","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T22:55:14Z","timestamp":1778194514000},"source":"Crossref","is-referenced-by-count":1,"title":["Modeling human B cell development with pluripotent stem cells"],"prefix":"10.64898","author":[{"given":"Xiaoning","family":"Sun","sequence":"first","affiliation":[{"name":"McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie J.","family":"Kwan","sequence":"additional","affiliation":[{"name":"McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Kothari","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Division of Immunology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra F.","family":"Nazzari","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Division of Immunology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Kosters","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Division of Immunology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin A.","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, University of Arizona College of Medicine, Tucson AZ 85724"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao Q.","family":"Thai","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, University of Arizona College of Medicine, Tucson AZ 85724"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepta","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, University of Arizona College of Medicine, Tucson AZ 85724"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Atkins","sequence":"additional","affiliation":[{"name":"McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin Chan","family":"Tung","sequence":"additional","affiliation":[{"name":"McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir T.","family":"Manchev","sequence":"additional","affiliation":[{"name":"McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Kennedy","sequence":"additional","affiliation":[{"name":"McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7258-906X","authenticated-orcid":false,"given":"Eliver","family":"Ghosn","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Division of Immunology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA"},{"name":"Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Keller","sequence":"additional","affiliation":[{"name":"McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto, ON M5G1L7, Canada"},{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050916551762000_2026.05.04.722674v1.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-074934"},{"key":"2026050916551762000_2026.05.04.722674v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-025-02757-y"},{"key":"2026050916551762000_2026.05.04.722674v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02283-3"},{"key":"2026050916551762000_2026.05.04.722674v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.11.012"},{"key":"2026050916551762000_2026.05.04.722674v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.09.001"},{"key":"2026050916551762000_2026.05.04.722674v1.6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190287"},{"key":"2026050916551762000_2026.05.04.722674v1.7","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aax0644"},{"key":"2026050916551762000_2026.05.04.722674v1.8","doi-asserted-by":"publisher","DOI":"10.1242\/dev.170571"},{"key":"2026050916551762000_2026.05.04.722674v1.9","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13198"},{"key":"2026050916551762000_2026.05.04.722674v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13192"},{"key":"2026050916551762000_2026.05.04.722674v1.11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700943"},{"key":"2026050916551762000_2026.05.04.722674v1.12","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001289"},{"key":"2026050916551762000_2026.05.04.722674v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo0510"},{"key":"2026050916551762000_2026.05.04.722674v1.14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.595"},{"key":"2026050916551762000_2026.05.04.722674v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nri3570"},{"key":"2026050916551762000_2026.05.04.722674v1.16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.8.1141"},{"key":"2026050916551762000_2026.05.04.722674v1.17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.5.1955"},{"key":"2026050916551762000_2026.05.04.722674v1.18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.4.1519"},{"key":"2026050916551762000_2026.05.04.722674v1.19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0800489"},{"key":"2026050916551762000_2026.05.04.722674v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/3877"},{"key":"2026050916551762000_2026.05.04.722674v1.21","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-093019-125603"},{"key":"2026050916551762000_2026.05.04.722674v1.22","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211924"},{"key":"2026050916551762000_2026.05.04.722674v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.127"},{"key":"2026050916551762000_2026.05.04.722674v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3161"},{"key":"2026050916551762000_2026.05.04.722674v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.11.003"},{"key":"2026050916551762000_2026.05.04.722674v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02360-7"},{"key":"2026050916551762000_2026.05.04.722674v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2915"},{"key":"2026050916551762000_2026.05.04.722674v1.28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-299941"},{"key":"2026050916551762000_2026.05.04.722674v1.29","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2014.0318"},{"key":"2026050916551762000_2026.05.04.722674v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26123-y"},{"key":"2026050916551762000_2026.05.04.722674v1.31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1649"},{"key":"2026050916551762000_2026.05.04.722674v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0445-8"},{"key":"2026050916551762000_2026.05.04.722674v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2615"},{"key":"2026050916551762000_2026.05.04.722674v1.34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-177139"},{"key":"2026050916551762000_2026.05.04.722674v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90077-9"},{"key":"2026050916551762000_2026.05.04.722674v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/376263a0"},{"key":"2026050916551762000_2026.05.04.722674v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90079-5"},{"key":"2026050916551762000_2026.05.04.722674v1.38","doi-asserted-by":"publisher","DOI":"10.1126\/science.2360047"},{"key":"2026050916551762000_2026.05.04.722674v1.39","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02500.x"},{"key":"2026050916551762000_2026.05.04.722674v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90293-L"},{"key":"2026050916551762000_2026.05.04.722674v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105123"},{"key":"2026050916551762000_2026.05.04.722674v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2005.11.001"},{"key":"2026050916551762000_2026.05.04.722674v1.43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1453"},{"key":"2026050916551762000_2026.05.04.722674v1.44","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-480244"},{"key":"2026050916551762000_2026.05.04.722674v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.02.010"},{"key":"2026050916551762000_2026.05.04.722674v1.46","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4049\/jimmunol.159.1.117","article-title":"TGF-beta down-regulates stromal IL-7 secretion and inhibits proliferation of human B cell precursors","volume":"159","year":"1997","journal-title":"J. Immunol"},{"key":"2026050916551762000_2026.05.04.722674v1.47","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011708"},{"key":"2026050916551762000_2026.05.04.722674v1.48","doi-asserted-by":"publisher","DOI":"10.64898\/2026.02.16.706247"},{"key":"2026050916551762000_2026.05.04.722674v1.49","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/5.12.1609"},{"key":"2026050916551762000_2026.05.04.722674v1.50","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113051"},{"key":"2026050916551762000_2026.05.04.722674v1.51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2239"},{"key":"2026050916551762000_2026.05.04.722674v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.12.019"},{"key":"2026050916551762000_2026.05.04.722674v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29356-8"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.04.722674","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T23:55:30Z","timestamp":1778370930000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.04.722674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":53,"URL":"https:\/\/doi.org\/10.64898\/2026.05.04.722674","relation":{},"subject":[],"published":{"date-parts":[[2026,5,7]]},"subtype":"preprint"}}