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Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes
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 neuroa...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216538/ https://www.ncbi.nlm.nih.gov/pubmed/34106998 http://dx.doi.org/10.1371/journal.ppat.1009618 |
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author | Soldan, Samantha S. Su, Chenhe Lamontagne, R. Jason Grams, Nicholas Lu, Fang Zhang, Yue Gesualdi, James D. Frase, Drew M. Tolvinski, Lois E. Martin, Kayla Messick, Troy E. Fingerut, Jonathan T. Koltsova, Ekaterina Kossenkov, Andrew Lieberman, Paul M. |
author_facet | Soldan, Samantha S. Su, Chenhe Lamontagne, R. Jason Grams, Nicholas Lu, Fang Zhang, Yue Gesualdi, James D. Frase, Drew M. Tolvinski, Lois E. Martin, Kayla Messick, Troy E. Fingerut, Jonathan T. Koltsova, Ekaterina Kossenkov, Andrew Lieberman, Paul M. |
author_sort | Soldan, Samantha S. |
collection | PubMed |
description | 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). |
format | Online Article Text |
id | pubmed-8216538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82165382021-07-01 Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes Soldan, Samantha S. Su, Chenhe Lamontagne, R. Jason Grams, Nicholas Lu, Fang Zhang, Yue Gesualdi, James D. Frase, Drew M. Tolvinski, Lois E. Martin, Kayla Messick, Troy E. Fingerut, Jonathan T. Koltsova, Ekaterina Kossenkov, Andrew Lieberman, Paul M. PLoS Pathog Research Article 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). Public Library of Science 2021-06-09 /pmc/articles/PMC8216538/ /pubmed/34106998 http://dx.doi.org/10.1371/journal.ppat.1009618 Text en © 2021 Soldan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Soldan, Samantha S. Su, Chenhe Lamontagne, R. Jason Grams, Nicholas Lu, Fang Zhang, Yue Gesualdi, James D. Frase, Drew M. Tolvinski, Lois E. Martin, Kayla Messick, Troy E. Fingerut, Jonathan T. Koltsova, Ekaterina Kossenkov, Andrew Lieberman, Paul M. Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes |
title | Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes |
title_full | Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes |
title_fullStr | Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes |
title_full_unstemmed | Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes |
title_short | Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes |
title_sort | epigenetic plasticity enables cns-trafficking of ebv-infected b lymphocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216538/ https://www.ncbi.nlm.nih.gov/pubmed/34106998 http://dx.doi.org/10.1371/journal.ppat.1009618 |
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