Activation of Naïve B Lymphocytes Via CD81, a Pathogenetic Mechanism for Hepatitis C Virus-associated B Lymphocyte Disorders

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Dec 13

PMID 16339892

Citations 108

Authors

Domenico Rosa

Giulietta Saletti

Ennio De Gregorio

Francesca Zorat

Consuelo Comar

Ugo DOro

Sandra Nuti

Michael Houghton

Vincenzo Barnaba

Gabriele Pozzato

Sergio Abrignani

Affiliations

Soon will be listed here.

Abstract

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-) 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+) 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 in vitro recapitulates the effects of HCV binding to B cell CD81 in vivo and that polyclonal proliferation of naïve B lymphocytes is a key initiating factor for the development of the HCV-associated B lymphocyte disorders.

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