{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:26Z","timestamp":1785422726133,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,2]]},"group-title":"Systems Biology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["75N93019C00071"],"award-info":[{"award-number":["75N93019C00071"]}]},{"award":["AI181898"],"award-info":[{"award-number":["AI181898"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U19AI135995"],"award-info":[{"award-number":["U19AI135995"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["W911NF-19-D-0001"],"award-info":[{"award-number":["W911NF-19-D-0001"]}],"id":[{"id":"https:\/\/ror.org\/05epdh915","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fairbairn Family Fund"},{"award":["P30-CA14051"],"award-info":[{"award-number":["P30-CA14051"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,2]]},"abstract":"<jats:p>While neutralizing ability has traditionally been considered the most important antibody function, appreciation has grown for Fc-mediated 'extra-neutralizing' functions, which are shaped by IgG glycosylation. However, there remain fundamental questions as to how B lymphocytes induce and regulate antibody glycosylation and thus functional capability. Understanding how transcriptional and cell state regulation shape glycosylation could reveal levers to tune protective humoral profiles in a disease- and antigen-specific manner. Prior studies have explored a limited panel of glycogenes and measured bulk glycosylation changes. Here, employing an in vitro antigen-specific B cell culture system, we systematically characterize transcriptional and humoral responses to cytokine perturbations. After exposure to a broad panel of cytokines (IL-4, IL-6, IL-10, IL-17, TNFa, IFNg, APRIL, and BAFF) across multiple concentrations and timepoints, transcriptomic profiling and lectin-based IgG glycome assays are employed to associate cytokine stimuli with both glycogene expression and IgG glycosylation. Supervised and unsupervised machine learning models identify cytokine-specific glycogene \"signatures\" as well as distinct immunoglobulin glycosylation profiles. We find that cytokines induce rapid transcriptional responses, with glycogene signatures outperforming single-gene changes in distinguishing stimulation conditions. We further demonstrate the ability to induce both pro- and anti-inflammatory IgG glycosylation profiles, particularly in terms of IgG galactosylation. This work demonstrates the utility of this system to parse the cytokine-driven regulation of B lymphocyte glycogenes, establishing a framework for dissecting how environmental cues shape antibody glycosylation, with relevance for autoimmune disease, infection, and vaccine responses.<\/jats:p>","DOI":"10.1101\/2025.09.30.679651","type":"posted-content","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:30:16Z","timestamp":1759451416000},"source":"Crossref","is-referenced-by-count":1,"title":["Multivariate analysis of glycogenes reveals coordinated regulation of immunoglobulin glycosylation in an immortalized human B cell system"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5022-2838","authenticated-orcid":false,"given":"Christine D","family":"Wiggins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sang\u00e9s Ametll\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin L","family":"Boswell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Koup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-989X","authenticated-orcid":false,"given":"Douglas A","family":"Lauffenburger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.30.679651","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:43:19Z","timestamp":1768470199000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.09.30.679651"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.09.30.679651","relation":{},"subject":[],"published":{"date-parts":[[2025,10,2]]},"subtype":"preprint"}}