HCV infection disturbs adaptive B cell responses

Poster number: 0

Sergio Abrignani

  1. National Institute of Molecular Genetics (INGM) Milan, Italy

The tetrasapanin CD81 associates to CD19 and CD21 on the surface of B lymphocytes to form a co-stimulatory complex that lowers the activation threshold when co-ligated to the B cell receptor (BCR). As CD81 binds the major envelope protein (E2) of the Hepatitis C virus (HCV) and it is the only known HCV receptor, we investigated the effect of CD81 engagement on B cell activation. We found that a combination of the HCV envelope protein E2 and an anti-CD81 monoclonal antibody leads to activation and proliferation of purified human B cells in vitro, in the absence of BCR co-ligation. Interestingly, CD81-mediated proliferation occurs preferentially in the naive (CD27-) B cell subset. CD81-mediated B cell activation does not require CD19 phosphorylation but depends on the c-Jun N-terminal kinase (JNK) signaling pathway. In parallel, we found that na´ve B lymphocytes from HCV infected patients display an increased expression of activation markers ex vivo, and that this phenotype normalizes after therapeutic eradication of HCV. The demonstration that CD81 engagement results in the polyclonal activation of na´ve B lymphocytes suggests a role for the CD81-E2 interaction in the pathogenesis of the B lymphocyte proliferative disorders associated to chronic HCV infection.