IgG-mediated enhancement of antibody responses is low in Fc receptor gammachain-deficient mice and increased in Fc gamma RII-deficient mice

Immunization with IgG/Ag or IgE/Ag complexes leads to a higher production o f specific Abs than immunization with Ag alone. The enhancing effect of IgE is exclusively dependent upon the low-affinity receptor for IgE, Fc epsilo n RII, whereas the mechanism behind IgG-mediated enhancement is unknown. We have investigated whether receptors for the Fc part of IgG are required fo r 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 g amma RIII-/-) were immunized with BSA-2,4,6-trinitrophenyl (TNP) alone or B SA-TNP complexed to monoclonal TNP-specific IgG1, IgG2a, or IgG2b, As expec ted, all subclasses enhanced the Ah-response to BSA in wild-type mice, Enha ncement was in the same order of magnitude in Fc gamma RIII-/- mice (less t han or equal to 177-fold of controls administered Ag alone), whereas it was abrogated in FcR gamma(-/-) mice and augmented in Fc gamma RII-/- mice (le ss than or equal to 5147-fold of controls). The response to IgE/Ag complexe s in FcR gamma(-/-) and Fc gamma RII-/- mice was similar to that seen for w ild-type mice, demonstrating that non-Fc gamma R-dependent responses were n ormal, Our observations suggest that IgG/Ag complexes enhance Ab responses via Fc gamma Rs, Moreover, they reveal a strong negative regulation of Ab r esponses to IgG/Ag exerted by Fc gamma RII.