Antibody Effector Functions Mediated by Fcγ-receptors Are Compromised During Persistent Viral Infection

Immunity. 2015 Feb 17;42(2):367-378. doi: 10.1016/j.immuni.2015.01.009. Epub 2015 Feb 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / pharmacology
  • Antibodies, Viral / immunology*
  • Antigen-Antibody Complex / immunology*
  • Antigens, CD20 / biosynthesis
  • Antigens, CD20 / immunology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Antigens / immunology
  • Dendritic Cells / immunology
  • Hypergammaglobulinemia / immunology
  • Immunologic Factors / pharmacology
  • Lymphocyte Activation / immunology
  • Lymphocyte Depletion*
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, IgG / immunology*
  • Rituximab

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Viral
  • Antigen-Antibody Complex
  • Antigens, CD20
  • CD40 Antigens
  • Immunologic Factors
  • Receptors, IgG
  • Rituximab