{"doi":"10.1101/2025.09.30.679651","title":"Multivariate analysis of glycogenes reveals coordinated regulation of immunoglobulin glycosylation in an immortalized human B cell system","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559199,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1460985,"name":"Marina Sangés Ametllé","orcid":null,"position":1,"is_corresponding":false},{"id":1371139,"name":"Chin‐Jen Wu","orcid":null,"position":2,"is_corresponding":false},{"id":564431,"name":"Kristin L. Boswell","orcid":"0000-0001-5264-3399","position":3,"is_corresponding":false},{"id":622852,"name":"Timothy A. Watkins","orcid":"0000-0002-1607-1335","position":4,"is_corresponding":false},{"id":290824,"name":"Richard A. Koup","orcid":"0000-0002-3090-7282","position":5,"is_corresponding":false},{"id":19320,"name":"Douglas A. Lauffenburger","orcid":"0000-0002-0050-989X","position":6,"is_corresponding":false},{"id":632131,"name":"Christine Davis","orcid":"0000-0002-5022-2838","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41256685","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}