Antibody effector functions mediated by Fcγ-receptors are compromised during persistent viral infection.

TitleAntibody effector functions mediated by Fcγ-receptors are compromised during persistent viral infection.
Publication TypeJournal Article
Year of Publication2015
AuthorsWieland A, Shashidharamurthy R, Kamphorst AO, Han J-H, Aubert RD, Choudhury BP, Stowell SR, Lee J, Punkosdy GA, Shlomchik MJ, Selvaraj P, Ahmed R
JournalImmunity
Volume42
Issue2
Pagination367-78
Date Published2015 Feb 17
ISSN1097-4180
Abstract

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.

DOI10.1016/j.immuni.2015.01.009
Alternate JournalImmunity
PubMed ID25680276
PubMed Central IDPMC4339104
Grant ListR01 AI030048 / AI / NIAID NIH HHS / United States
R01 AR044077 / AR / NIAMS NIH HHS / United States
R01 CA138993 / CA / NCI NIH HHS / United States
R01-AI030048 / AI / NIAID NIH HHS / United States
R01-AR044077 / AR / NIAMS NIH HHS / United States
R01-CA138993 / CA / NCI NIH HHS / United States
T32 AI070081 / AI / NIAID NIH HHS / United States
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