{"doi":"10.1016/j.celrep.2020.107815","title":"CD28 Regulates Metabolic Fitness for Long-Lived Plasma Cell Survival","abstract":"Durable humoral immunity against epidemic infectious disease requires the survival of long-lived plasma cells (LLPCs). LLPC longevity is dependent on metabolic programs distinct from short-lived plasma cells (SLPCs); however, the mechanistic basis for this difference is unclear. We have previously shown that CD28, the prototypic T cell costimulatory receptor, is expressed on both LLPCs and SLPCs but is essential only for LLPC survival. Here we show that CD28 transduces pro-survival signaling specifically in LLPCs through differential SLP76 expression. CD28 signaling in LLPCs increased glucose uptake, mitochondrial mass/respiration, and reactive oxygen species (ROS) production. Unexpectedly, CD28-mediated regulation of mitochondrial respiration, NF-κB activation, and survival was ROS dependent. IRF4, a target of NF-κB, was upregulated by CD28 activation in LLPCs and decreased IRF4 levels correlated with decreased glucose uptake, mitochondrial mass, ROS, and CD28-mediated survival. Altogether, these data demonstrate that CD28 signaling induces a ROS-dependent metabolic program required for LLPC survival.","journal":"Cell Reports","year":2020,"id":66435,"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":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"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":351776,"name":"Colin Chavel","orcid":"0000-0003-1458-8979","position":1,"is_corresponding":false},{"id":351777,"name":"Shivana M. Lightman","orcid":"0000-0003-0810-6515","position":2,"is_corresponding":false},{"id":351778,"name":"G. Aaron Holling","orcid":"0000-0001-5747-2592","position":3,"is_corresponding":false},{"id":351779,"name":"James J. M. Cooper","orcid":"0000-0002-4760-2784","position":4,"is_corresponding":false},{"id":72012,"name":"Peng Peng","orcid":"0000-0002-8170-8961","position":5,"is_corresponding":false},{"id":351780,"name":"Wensheng Liu","orcid":"0000-0001-9621-2742","position":6,"is_corresponding":false},{"id":28922,"name":"Benjamin G. Barwick","orcid":"0000-0001-9810-3566","position":7,"is_corresponding":false},{"id":352484,"name":"Catherine M. Gavile","orcid":null,"position":8,"is_corresponding":false},{"id":351781,"name":"Orla Maguire","orcid":"0000-0003-0544-560X","position":9,"is_corresponding":false},{"id":352485,"name":"Megan Murray-Dupuis","orcid":null,"position":10,"is_corresponding":false},{"id":352486,"name":"Cheryl Rozanski","orcid":null,"position":11,"is_corresponding":false},{"id":296325,"name":"Martha S. Jordan","orcid":"0000-0003-2359-3227","position":12,"is_corresponding":false},{"id":264135,"name":"Taku Kambayashi","orcid":"0000-0002-6753-3181","position":13,"is_corresponding":false},{"id":351782,"name":"Scott H. Olejniczak","orcid":"0000-0001-6857-5554","position":14,"is_corresponding":false},{"id":28928,"name":"Lawrence Boise","orcid":"0000-0001-9436-8815","position":15,"is_corresponding":false},{"id":351783,"name":"Kelvin P. Lee","orcid":"0000-0003-2587-0734","position":16,"is_corresponding":false},{"id":352483,"name":"Adam Utley","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T21:14:22.090509Z","pmid":"32579940","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":[]}