Enhanced apoptosis of peripheral CD5-negative B lymphocytes from chronically hepatitis C virus-infected patients: reversal after antiviral treatment.

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-kappaB 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-kappaB expression and was found only in CD5-negative (CD5(neg)) B cells, whereas CD5(pos) 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 CD5(pos) B-cell subpopulation to apoptosis may play a role in HCV-related autoimmunity and lymphoproliferation.