Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile
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
Affiliations
Amanda N. Henning
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Myagmarjav Budeebazar
Department of Gastroenterology, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; Liver Center, Ulaanbaatar 14230, Mongolia
Delgerbat Boldbaatar
Liver Center, Ulaanbaatar 14230, Mongolia
Dahgwahdorj Yagaanbuyant
Liver Center, Ulaanbaatar 14230, Mongolia
Davaadorj Duger
Department of Gastroenterology, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
Khishigjargal Batsukh
Center of Hematology and Bone Marrow Transplantation, First Central Hospital of Mongolia, Ulaanbaatar 14210, Mongolia
Huizhi Zhou
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Ryan Baumann
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Robert D. Allison
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Harvey J. Alter
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Naranjargal Dashdorj
Liver Center, Ulaanbaatar 14230, Mongolia; Onom Foundation, Ulaanbaatar 17011, Mongolia
Valeria De Giorgi
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
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.
