Title

Antibody Effector Functions Mediated by FcY-Receptors Are Compromised during Persistent Viral Infection

Document Type

Article

Publication Date

2015

Abstract

Summary T cell dysfunction is well documented during chronic viral infections but little is known about functional abnormalities in humoral immunity. Here we report that mice persistently infected with lymphocytic choriomeningitis virus (LCMV) exhibit a severe defect in Fcγ-receptor (FcγR)-mediated antibody effector functions. Using transgenic mice expressing human CD20, we found that chronic LCMV infection impaired the depletion of B cells with rituximab, an anti-CD20 antibody widely used for the treatment of B cell lymphomas. In addition, FcγR-dependent activation of dendritic cells by agonistic anti-CD40 antibody was compromised in chronically infected mice. These defects were due to viral antigen-antibody complexes and not the chronic infection per se, because FcγR-mediated effector functions were normal in persistently infected mice that lacked LCMV-specific antibodies. Our findings have implications for the therapeutic use of antibodies and suggest that high levels of pre-existing immune complexes could limit the effectiveness of antibody therapy in humans.

Publication Title

Immunity

Volume

42

Issue

2

First Page

367

Last Page

378

Comments

This article was published in Immunity, Volume 42, Issue 2, Pages 367-378.

The published version is available at http://dx.doi.org/10.1016/j.immuni.2015.01.009.

Copyright © 2015 Elsevier.

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