Pre-stimulation of CD81 expression by resting B cells increases proliferation following EBV infection, but the overexpression of CD81 induces the apoptosis of EBV-transformed B cells.
Hepatitis C virus (HCV) E2 protein binds to CD81, which is a component of the B cell co-stimulatory complex. The E2-CD81 interaction leads to B cell proliferation, protein tyrosine phosphorylation and to the hypermutation of immunoglobulin genes. Epidemiological studies have reported a high prevalence of B cell non-Hodgkin lymphoma (NHL) in HCV-positive patients, suggesting a potential association between HCV and Epstein-Barr virus (EBV) in the genesis of B lymphocyte proliferative disorders. In the present study, in order to investigate the association between EBV and HCV in B cells, we created an in vitro EBV-induced B cell transformation model. CD81 was gradually overexpressed during transformation by EBV. B cells isolated from HCV-positive patients grew more rapidly and clumped together earlier than B cells isolated from healthy donors following EBV infection. Pre-stimulation of CD81 expressed by resting B cells with anti-CD81 monoclonal antibody (mAb) or HCV E2 accelerated the generation of lymphoblastoid cell lines (LCLs) by EBV infection. These cells proliferated prominently through the early expression of interleukin-10 and intracellular latent membrane protein (LMP)-l. By contrast, the overexpression of CD81 on EBV-transformed B cells by anti-CD81 mAb or HCV E2 protein induced apoptosis through reactive oxygen species (ROS)-mediated mitochondrial dysfunction. These results suggest that the engagement of CD81 expressed by B cells has differential effects on B cell fate (proliferation or apoptosis) according to EBV infection and the expression level of CD81.
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Ga Bin
GB
Park
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Daejin
D
Kim
Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
Sung Jae
SJ
Park
Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
Hyun-Kyung
HK
Lee
Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
Ji Hyun
JH
Kim
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Yeong Seok
YS
Kim
Department of Microbiology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Sae-Gwang
SG
Park
Department of Microbiology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
In-Hak
IH
Choi
Department of Plastic Surgery, Inje University Haeundae Paik Hospital, Busan 614-735, Republic of Korea.
Sung Ho
SH
Yoon
Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
Youn Jae
YJ
Lee
Department of Neurosurgery, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
Sunghwa
S
Paeng
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Dae Young
DY
Hur
D000328:Adult; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015153:Blotting, Western; D049109:Cell Proliferation; D002472:Cell Transformation, Viral / Q000276:immunology*; D002478:Cells, Cultured; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005260:Female; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology; D006526:Hepatitis C / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000276:immunology; D018613:Microscopy, Confocal; D008875:Middle Aged; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060225:Tetraspanin 28 / Q000276:immunology* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; C554798:CD81 protein, human; D017382:Reactive Oxygen Species; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus