Increased killer B cells in chronic HCV infection may lead to autoimmunity and increased viral load

Abstract

Regulatory B (Breg ) cells are characterized by various membrane markers and the secretion of different inhibitory cytokines. A new subset of Breg cells was identified as CD5hi Fas-ligand (FasL)hi . Their main reported role is to suppress anti-viral and anti-tumour immune responses, and, hence they have been dubbed 'killer' B cells. In this study, we aim to assess the role of these cells in chronic hepatitis C virus (HCV) infection, and determine if they contribute to the increased viral load and persistence of HCV and its related autoimmunity. (i) FasL expression on CD5hi B cells is increased significantly in HCV-infected patients compared to healthy individuals [28·06±6·71 mean fluorescence intensity (MFI)±standard error of the mean (s.e.m.), median = 27·9 versus 10·87±3·97 MFI±s.e.m., median = 10·3, respectively, P<0·0001]. (ii) Killer B cells from HCV patients increased autologous CD4+ T cell apoptosis compared to the apoptosis in healthy individuals [39·17%±7·18% mean±standard deviation (s.d.), median = 39·6 versus 25·92±8·65%, mean±s.d., median = 24·1%, P<0·0001, respectively]. A similar increase was observed in CD8+ T cell apoptosis (54·67±15·49% mean±s.d., median=57·3 versus 21·07%±7·4%, mean±s.d., median=20%, P=0·0006, respectively). (iii) By neutralizing FasL with monoclonal anti-FasL antibodies, we have shown that the induction of apoptosis by killer B cells is FasL-dependent. (iv) Increased expression of FasL on CD5hi B cells is correlated positively with an increased viral load and the presence of anti-nuclear antibodies and rheumatoid factor in HCV. This is the first study in which killer B cells have been suggested to play a pathogenic role in HCV. They seem to be involved in HCV's ability to escape efficient immune responses.