{"doi":"10.1371/journal.ppat.1009618","title":"Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes","abstract":"Subpopulations of B-lymphocytes traffic to different sites and organs to provide diverse and tissue-specific functions. Here, we provide evidence that epigenetic differences confer a neuroinvasive phenotype. An EBV+ B cell lymphoma cell line (M14) with low frequency trafficking to the CNS was neuroadapted to generate a highly neuroinvasive B-cell population (MUN14). MUN14 B cells efficiently infiltrated the CNS within one week and produced neurological pathologies. We compared the gene expression profiles of viral and cellular genes using RNA-Seq and identified one viral (EBNA1) and several cellular gene candidates, including secreted phosphoprotein 1/osteopontin (SPP1/OPN), neuron navigator 3 (NAV3), CXCR4, and germinal center-associated signaling and motility protein (GCSAM) that were selectively upregulated in MUN14. ATAC-Seq and ChIP-qPCR revealed that these gene expression changes correlated with epigenetic changes at gene regulatory elements. The neuroinvasive phenotype could be attenuated with a neutralizing antibody to OPN, confirming the functional role of this protein in trafficking EBV+ B cells to the CNS. These studies indicate that B-cell trafficking to the CNS can be acquired by epigenetic adaptations and provide a new model to study B-cell neuroinvasion associated CNS lymphoma and autoimmune disease of the CNS, including multiple sclerosis (MS).","journal":"PLoS Pathogens","year":2021,"id":167941,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":667141,"name":"Chenhe Su","orcid":null,"position":1,"is_corresponding":false},{"id":666213,"name":"Jason Lamontagne","orcid":"0000-0002-9068-3348","position":2,"is_corresponding":false},{"id":428887,"name":"Nicholas Grams","orcid":"0000-0002-3107-143X","position":3,"is_corresponding":false},{"id":299549,"name":"Fang Lü","orcid":"0000-0002-0570-7801","position":4,"is_corresponding":false},{"id":360718,"name":"Yue Zhang","orcid":"0000-0002-6612-8002","position":5,"is_corresponding":false},{"id":694032,"name":"James Gesualdi","orcid":"0000-0002-7846-2761","position":6,"is_corresponding":false},{"id":360716,"name":"Drew Frase","orcid":"0000-0003-3129-4673","position":7,"is_corresponding":false},{"id":378069,"name":"Lois Tolvinski","orcid":"0000-0001-7313-0103","position":8,"is_corresponding":false},{"id":697208,"name":"Kayla Martin","orcid":null,"position":9,"is_corresponding":false},{"id":378068,"name":"Troy E. Messick","orcid":"0000-0001-7914-1524","position":10,"is_corresponding":false},{"id":696337,"name":"Jonathan T. Fingerut","orcid":"0000-0003-4285-1957","position":11,"is_corresponding":false},{"id":577435,"name":"Ekaterina K. Koltsova","orcid":"0000-0001-9872-9905","position":12,"is_corresponding":false},{"id":245076,"name":"Andrew V. Kossenkov","orcid":"0000-0002-1536-0418","position":13,"is_corresponding":false},{"id":299552,"name":"Paul M. Lieberman","orcid":"0000-0002-3935-9921","position":14,"is_corresponding":false},{"id":348685,"name":"Samantha S. Soldan","orcid":"0000-0001-6263-519X","position":0,"is_corresponding":true}],"reference_count":111,"raw_metadata":null,"created_at":"2026-07-18T23:46:02.603031Z","pmid":"34106998","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":[]}