Analysis of B‐lymphocyte differentiation in patients infected with hepatitis C virus

To clarify whether some of the functions of B lymphocytes could be affected during hepatitis C virus (HCV) infection, phenotypic characteristics of B lymphocytes from HCV‐infected patients and their capacity to differentiate into immunoglobulins (Ig)‐secreting cells were studied. B lymphocytes differentiation was investigated for patients untreated and non‐responders (n = 9), treated and non‐responders (n = 6), responders (n = 6), long‐term responders (n = 9) to therapy and seronegative controls (n = 14) following in vitro stimulation with S. aureus strain Cowan I mitogen. HCV sequences in purified B lymphocytes were detected by RT‐PCR. It was found that HCV‐patients harbor a similar mean percentage of B cells and a normal level of naïve B cells (% IgM+/IgD+ cells = 79.7 ± 15.4 for untreated non‐responders, 57.1 ± 22.9 for treated non‐responders, 44.3 ± 29.1 for responders, 75.7 ± 16 for long‐term responders) as compared with controls. It was also found that peripheral blood mononuclear cells (PBMCs) of patients or controls produced similar amounts of IgG, A, and M in vitro. A total of 57% of untreated non‐responders versus 17% of treated non‐responders were able to produce HCV‐specific antibodies. Interestingly, B lymphocytes from PBMCs able to secrete anti‐HCV antibodies contained HCV positive strand RNA, although no systematic detection of the negative strand was found. These data suggest that signaling through the B cell receptor (BCR) in B lymphocytes of HCV‐infected patients appears normal whatever their response to therapy. The capacity to secrete HCV‐specific IgG seemed to be linked to the presence of positive strand RNA rather than virus replication. J. Med. Virol. 72:566–574, 2004. © 2004 Wiley‐Liss, Inc.