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• W2802362212 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. In our study, we found Killer B cells, a subset of B regulatory cells (CD19+CD5hiFasLhi) to be increased in HCV patients when compared to healthy controls and in correlation with increased autoimmunity in these patients. The co-culture of killer B cells with autologous CD4 or CD8 T cells increases the rate of T cells apoptosis, mainly in HCV patients, in a Fas-FasL dependent mechanism." @default.
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• W2802362212 date "2018-07-15" @default.
• W2802362212 modified "2023-10-14" @default.
• W2802362212 title "Increased killer B cells in chronic HCV infection may lead to autoimmunity and increased viral load" @default.
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• W2802362212 doi "https://doi.org/10.1111/cei.13139" @default.
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