IgG3-mediated enhancement of the antibody response is normal in Fc gammaRI-deficient mice.
Antibodies, administered together with their specific antigen, can feedback-regulate antibody responses to this antigen. IgG1, IgG2a and IgG2b enhance antibody responses to soluble protein antigens. This effect is primarily mediated by FcRs as enhancement is impaired in FcR gamma-/- mice, reported to lack Fc gammaRI and Fc gammaRIII because of deletion of the common FcR gamma chain. Also IgG3 can enhance antibody responses. However, this effect is unperturbed in FcR gamma-/- mice but severely impaired in complement-depleted animals and in animals lacking complement receptor 1 and 2. Although this argues against involvement of Fc gammaRs, FcR gamma-/- mice may express one-fifth of the normal levels of Fc gammaRI and, in addition, Fc gammaRI has been suggested to bind IgG3. We re-investigated the dependence of IgG3-mediated enhancement on Fc gammaRs using a mouse strain selectively lacking Fc gammaRI and found that IgG3-mediated enhancement is completely normal. Unlike IgE and IgG2a, which are both thought to enhance T-cell proliferation via FcR-mediated antigen presentation, IgG3 was a poor enhancer of T-cell proliferation both in vivo and in vitro. These findings argue against a significant involvement of Fc gammaRs in IgG3-mediated enhancement of antibody responses and support our previous conclusion that complement plays a major role.
Hjelm
F
F
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Carlsson
F
F
Verbeek
S
S
Heyman
B
B
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010851:Picrates / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D014611:Vaccination
C485701:Fcgr1 protein, mouse; D007074:Immunoglobulin G; D010851:Picrates; D017452:Receptors, IgG; D010047:Ovalbumin; D006433:Hemocyanins; C005858:picric acid; C032808:keyhole-limpet hemocyanin