IgG-mediated enhancement of antibody responses is low in Fc receptor gamma chain-deficient mice and increased in Fc gamma RII-deficient mice.
Immunization with IgG/Ag or IgE/Ag complexes leads to a higher production of specific Abs than immunization with Ag alone. The enhancing effect of IgE is exclusively dependent upon the low-affinity receptor for IgE, Fc epsilon RII, whereas the mechanism behind IgG-mediated enhancement is unknown. We have investigated whether receptors for the Fc part of IgG are required for responses to IgG/Ag. Mice lacking the gamma subunit of Fc receptors (FcRs) (FcR gamma-/-), Fc gamma RII (Fc gamma RII-/-), or Fc gamma RIII (Fc gamma RIII-/-) were immunized with BSA-2,4,6-trinitrophenyl (TNP) alone or BSA-TNP complexed to monoclonal TNP-specific IgG1, IgG2a, or IgG2b. As expected, all subclasses enhanced the Ab-response to BSA in wild-type mice. Enhancement was in the same order of magnitude in Fc gamma RIII-/- mice (</=177-fold of controls administered Ag alone), whereas it was abrogated in FcR gamma-/- mice and augmented in Fc gamma RII-/- mice (</=5147-fold of controls). The response to IgE/Ag complexes in FcR gamma-/- and Fc gamma RII-/- mice was similar to that se for wild-type mice, demonstrating that non-Fc gamma R-dependent responses were normal. Our observations suggest that IgG/Ag complexes enhance Ab responses via Fc gamma Rs. Moreover, they reveal a strong negative regulation of Ab responses to IgG/Ag exerted by Fc gamma RII.
Department of Genetics and Pathology, Uppsala University, Sweden.
S
S
Wernersson
M C
MC
Karlsson
J
J
Dahlström
R
R
Mattsson
J S
JS
Verbeek
B
B
Heyman
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology; D007074:Immunoglobulin G / Q000502:physiology*; D007136:Immunoglobulins / Q000096:biosynthesis*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000276:immunology; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D014443:Tyrosine / Q000276:immunology
D000276:Adjuvants, Immunologic; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007136:Immunoglobulins; D010446:Peptide Fragments; D017452:Receptors, IgG; D014443:Tyrosine