imprint:
Proceedings of the National Academy of Sciences, 2005
Published in:Proceedings of the National Academy of Sciences
Language:
English
DOI:
10.1073/pnas.0509402102
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
<jats:p>Infection with hepatitis C virus (HCV), a leading cause of chronic liver diseases, can associate with B lymphocyte proliferative disorders, such as mixed cryoglobulinemia and non-Hodgkin lymphoma. The major envelope protein of HCV (HCV-E2) binds, with high affinity CD81, a tetraspanin expressed on several cell types. Here, we show that engagement of CD81 on human B cells by a combination of HCV-E2 and an anti-CD81 mAb triggers the JNK pathway and leads to the preferential proliferation of the naïve (CD27<jats:sup>-</jats:sup>) B cell subset. In parallel, we have found that B lymphocytes from the great majority of chronic hepatitis C patients are activated and that naïve cells display a higher level of activation markers than memory (CD27<jats:sup>+</jats:sup>) B lymphocytes. Moreover, eradication of HCV infection by IFN therapy is associated with normalization of the activation-markers expression. We propose that CD81-mediated activation of B cells<jats:italic>in vitro</jats:italic>recapitulates the effects of HCV binding to B cell CD81<jats:italic>in vivo</jats:italic>and that polyclonal proliferation of naïve B lymphocytes is a key initiating factor for the development of the HCV-associated B lymphocyte disorders.</jats:p>