Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile

Summary: Chronic HCV infection remains a global health concern due to its involvement in hepatic and extrahepatic diseases, including B cell non-Hodgkin lymphoma (BNHL). Clinical and epidemiological evidence support a causal role for HCV in BNHL development, although mechanistic insight is lacking....

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Main Authors: Amanda N. Henning, Myagmarjav Budeebazar, Delgerbat Boldbaatar, Dahgwahdorj Yagaanbuyant, Davaadorj Duger, Khishigjargal Batsukh, Huizhi Zhou, Ryan Baumann, Robert D. Allison, Harvey J. Alter, Naranjargal Dashdorj, Valeria De Giorgi
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222020740
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author Amanda N. Henning
Myagmarjav Budeebazar
Delgerbat Boldbaatar
Dahgwahdorj Yagaanbuyant
Davaadorj Duger
Khishigjargal Batsukh
Huizhi Zhou
Ryan Baumann
Robert D. Allison
Harvey J. Alter
Naranjargal Dashdorj
Valeria De Giorgi
author_facet Amanda N. Henning
Myagmarjav Budeebazar
Delgerbat Boldbaatar
Dahgwahdorj Yagaanbuyant
Davaadorj Duger
Khishigjargal Batsukh
Huizhi Zhou
Ryan Baumann
Robert D. Allison
Harvey J. Alter
Naranjargal Dashdorj
Valeria De Giorgi
author_sort Amanda N. Henning
collection DOAJ
description Summary: Chronic HCV infection remains a global health concern due to its involvement in hepatic and extrahepatic diseases, including B cell non-Hodgkin lymphoma (BNHL). Clinical and epidemiological evidence support a causal role for HCV in BNHL development, although mechanistic insight is lacking. We performed RNA-sequencing on peripheral B cells from patients with HCV alone, BNHL alone, and HCV-associated BNHL to identify unique and shared transcriptional profiles associated with transformation. In patients with HCV-associated BNHL, we observed the enrichment of an anergic-like gene signature and evidence of clonal expansion that was correlated with the expression of epigenetic regulatory genes. Our data support a role for viral-mediated clonal expansion of anergic-like B cells in HCV-associated BNHL development and suggest epigenetic dysregulation as a potential mechanism driving expansion. We propose epigenetic mechanisms may be involved in both HCV-associated lymphoma and regulation of B cell anergy, representing an attractive target for clinical interventions.
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spelling doaj.art-ff30ba90c541428bb1b29db39acc57162023-01-22T04:41:04ZengElsevieriScience2589-00422023-01-01261105801Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profileAmanda N. Henning0Myagmarjav Budeebazar1Delgerbat Boldbaatar2Dahgwahdorj Yagaanbuyant3Davaadorj Duger4Khishigjargal Batsukh5Huizhi Zhou6Ryan Baumann7Robert D. Allison8Harvey J. Alter9Naranjargal Dashdorj10Valeria De Giorgi11Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding authorDepartment of Gastroenterology, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; Liver Center, Ulaanbaatar 14230, MongoliaLiver Center, Ulaanbaatar 14230, MongoliaLiver Center, Ulaanbaatar 14230, MongoliaDepartment of Gastroenterology, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, MongoliaCenter of Hematology and Bone Marrow Transplantation, First Central Hospital of Mongolia, Ulaanbaatar 14210, MongoliaDepartment of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USADepartment of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USABloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USALiver Center, Ulaanbaatar 14230, Mongolia; Onom Foundation, Ulaanbaatar 17011, MongoliaDepartment of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding authorSummary: Chronic HCV infection remains a global health concern due to its involvement in hepatic and extrahepatic diseases, including B cell non-Hodgkin lymphoma (BNHL). Clinical and epidemiological evidence support a causal role for HCV in BNHL development, although mechanistic insight is lacking. We performed RNA-sequencing on peripheral B cells from patients with HCV alone, BNHL alone, and HCV-associated BNHL to identify unique and shared transcriptional profiles associated with transformation. In patients with HCV-associated BNHL, we observed the enrichment of an anergic-like gene signature and evidence of clonal expansion that was correlated with the expression of epigenetic regulatory genes. Our data support a role for viral-mediated clonal expansion of anergic-like B cells in HCV-associated BNHL development and suggest epigenetic dysregulation as a potential mechanism driving expansion. We propose epigenetic mechanisms may be involved in both HCV-associated lymphoma and regulation of B cell anergy, representing an attractive target for clinical interventions.http://www.sciencedirect.com/science/article/pii/S2589004222020740EpigeneticsImmunologyVirology
spellingShingle Amanda N. Henning
Myagmarjav Budeebazar
Delgerbat Boldbaatar
Dahgwahdorj Yagaanbuyant
Davaadorj Duger
Khishigjargal Batsukh
Huizhi Zhou
Ryan Baumann
Robert D. Allison
Harvey J. Alter
Naranjargal Dashdorj
Valeria De Giorgi
Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile
iScience
Epigenetics
Immunology
Virology
title Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile
title_full Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile
title_fullStr Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile
title_full_unstemmed Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile
title_short Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile
title_sort peripheral b cells from patients with hepatitis c virus associated lymphoma exhibit clonal expansion and an anergic like transcriptional profile
topic Epigenetics
Immunology
Virology
url http://www.sciencedirect.com/science/article/pii/S2589004222020740
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