{"doi":"10.1101/2020.02.16.947408","title":"Organoid Polymer Functionality and Mode of <i>Klebsiella Pneumoniae</i> Membrane Antigen Presentation Regulates Ex Vivo Germinal Center Epigenetics in Young and Aged B Cells","abstract":"Abstract Antibiotic-resistant bacteria are a major global health threat that continues to rise due to a lack of effective vaccines. Of concern are Klebsiella pneumoniae that fail to induce in vivo germinal center B cell responses, which facilitate antibody production to fight infection. Immunotherapies using antibodies targeting antibiotic-resistant bacteria are emerging as promising alternatives, however, cannot be efficiently derived ex vivo, necessitating the need for immune technologies to develop therapeutics. Here, four-arm PEG-organoids were developed to elucidate the effects of polymer end-point chemistry, integrin ligands, and mode of K. pneumoniae antigen presentation on germinal center-like B cell epigenetics, to better define the cell-microenvironment factors regulating ex vivo germinal center dynamics. Notably, PEG vinyl sulfone or acrylate failed to sustain primary immune cells, but functionalization with maleimide (PEG-4MAL) led to B cell expansion and germinal center-like induction. RNA sequencing analysis of lymph node stromal and germinal center B cells showed niche associated heterogeneity of integrin-related genes. Incorporation of niche-mimicking bioadhesive peptides revealed that collagen 1 mimicking peptides promoted germinal center-like dynamics and epigenetics. PEG-4MAL organoids elucidated the impact of K. pneumoniae membrane embedded protein antigen versus soluble antigen presentation on germinal center-like activation and preserved the response across young and aged mice.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":128918,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":494087,"name":"Kristine Lai","orcid":"0000-0002-1950-0668","position":1,"is_corresponding":false},{"id":494088,"name":"Sarah E. Post","orcid":"0000-0002-7965-3949","position":2,"is_corresponding":false},{"id":240594,"name":"Ilana Brito","orcid":"0000-0002-2250-3480","position":3,"is_corresponding":false},{"id":235419,"name":"Jason G. Cyster","orcid":"0000-0002-4735-9745","position":4,"is_corresponding":false},{"id":254092,"name":"Ankur Singh","orcid":"0000-0002-3501-2277","position":5,"is_corresponding":false},{"id":494086,"name":"Pamela L. Graney","orcid":"0000-0003-0428-2634","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:15:42.522809Z","pmid":null,"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":[]}