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Journal of Virology, October 2004, p. 11379-11384, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11379-11384.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Enhanced Apoptosis of Peripheral CD5-Negative B Lymphocytes from Chronically Hepatitis C Virus-Infected Patients: Reversal after Antiviral Treatment

Elias Toubi,1* Aharon Kessel,1 Regina Peri,1 Zehava Shmuel,1 Ellen Bamberger,2 Edmond Sabo,1 and Eli Zuckerman2

Division of Clinical Immunology and Allergy,1 The Liver Unit, Internal Medicine A Bnai Zion Medical Center, Haifa, Israel2

Received 26 January 2004/ Accepted 3 June 2004

Whereas enhanced peripheral T-cell apoptosis and its association with autoimmunity have recently been reported, the apoptotic status of peripheral B cells in chronic hepatitis C virus (HCV) infection remains ambiguous. We therefore sought to investigate the sensitivity of peripheral B cells to apoptosis and to assess the possible benefits of antiviral treatment in mitigating these effects. Spontaneous apoptosis, the extent of apoptosis rescue, and NF-{kappa}B expression in peripheral B cells were studied in patients with chronic HCV infections (group 1), in sustained responders after antiviral treatment (group 2), and in healthy controls (group 3). For group 1, spontaneous B-cell apoptosis was increased (26% ± 4.6%) and apoptosis rescue was altered (39%) compared to group 3 (18% ± 5% and 50%, respectively; P = 0.001). In contrast, apoptosis and apoptosis rescue were similar for groups 2 and 3. Enhanced B-cell apoptosis was associated with decreased NF-{kappa}B expression and was found only in CD5-negative (CD5neg) B cells, whereas CD5pos cells were apoptosis resistant. Chronic HCV infection is associated with enhanced peripheral B-cell apoptosis and decreased apoptosis rescue. Successful antiviral treatment reverses these abnormalities to the levels seen in healthy individuals. The relative resistance of the CD5pos B-cell subpopulation to apoptosis may play a role in HCV-related autoimmunity and lymphoproliferation.

* Corresponding author. Mailing address: Division of Clinical Immunology and Allergy, Bnai Zion Medical Center, Golomb St. 47, P.O.B. 4940, Haifa 31048, Israel. Phone: 972-4-8359659. Fax: 972-4-8371393. E-mail: e.toubi{at}b-zion.org.il.

Journal of Virology, October 2004, p. 11379-11384, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11379-11384.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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