A recombinant
polypeptide corresponding to a virus-specific
cDNA clone (c100-3) serves as the
antigen for a hepatitis C virus (HCV) antibody assay. Previous investigations have shown an 80% prevalence of
HCV antibodies in sera of patients suffering from post-transfusional
chronic hepatitis non-A, non-B, but positive results were also obtained for 30 to 70% of sera from patients with
chronic hepatitis B or
autoimmune hepatitis. In this study we show that
HCV antibodies are secreted by peripheral blood lymphocytes (PBL) in vitro. PBL from 12/35 patients with chronic non-A, non-B
hepatitis and 1/6 patients with
chronic active hepatitis B spontaneously secreted
HCV antibodies in cell culture supernatants. The results were confirmed by neutralisation assay and ELISAs using recombinant and synthetic
polypeptides derived from the c100-3
antigen and from the HCV core
antigen. Two patients suffering from non-A, non-B
hepatitis were negative for
HCV antibodies in serum, but their PBL produced HCV c100-3
antibodies in vitro. PBL from patients suffering from
autoimmune chronic hepatitis,
primary biliary cirrhosis, toxic-liver injury and healthy blood donors did not produce
antibodies to HCV c100
antigen irrespective of HCV antibody test results in their sera. Polyclonal B cell activation or mitogenic stimulation of T helper cells led to increased
immunoglobulin synthesis by PBL in vitro, but did not lead to enhancement of specific HCV antibody production. In addition, HCV antibody production was not induced by these stimulation procedures in control lymphocytes. This spontaneous HCV antibody production in vitro suggests persistent antigenic stimulation of the B cells in vivo.