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

Park,Ga  Bin; Kim,Daejin; Park,Sung  Jae; Lee,Hyun-Kyung; Kim,Ji  Hyun; Kim,Yeong  Seok; Park,Sae-Gwang; Choi,In-Hak; Yoon,Sung  Ho; Lee,Youn  Jae; Paeng,Sunghwa; Hur,Dae  Young

doi:10.3892/ijmm.2015.2372

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

Authors:
- Ga Bin Park
- Daejin Kim
- Sung Jae Park
- Hyun-Kyung Lee
- Ji Hyun Kim
- Yeong Seok Kim
- Sae-Gwang Park
- In-Hak Choi
- Sung Ho Yoon
- Youn Jae Lee
- Sunghwa Paeng
- Dae Young Hur
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Affiliations: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea, Department of Microbiology, Inje University College of Medicine, Busan 614-735, Republic of Korea, Department of Plastic Surgery, Inje University Haeundae Paik Hospital, Busan 614-735, Republic of Korea, Department of Neurosurgery, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea
Published online on: October 13, 2015 https://doi.org/10.3892/ijmm.2015.2372
Pages: 1464-1478
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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