A role for complement in feedback enhancement of antibody responses by IgG3.
IgG1, IgG2a, and IgG2b, passively administered with soluble Ags, enhance specific Ab responses. The effect of IgG3 in this type of feedback regulation has not been studied previously. We immunized mice with trinitrophenyl (TNP)-coupled carrier proteins (bovine serum albumin [BSA] or ovalbumin [OVA]) alone or complexed to monoclonal TNP-specific IgG3. The carrier-specific Ab responses were enhanced by several hundred-fold by IgG3. Enhancement was significantly impaired in mice depleted of complement factor C3 and in mice lacking complement receptors 1 and 2 (Cr2-/-). In contrast, mice lacking the common Fc-receptor gamma chain (FcR gamma -/-), resulting in reduced expression of Fc gamma RI and lack of Fc gamma RIII, and mice lacking Fc gamma RIIB (Fc gamma RIIB-/-), responded equally well to immunization with IgG3-complexed Ag as wild-type controls. These findings demonstrate that IgG3 can induce feedback enhancement and that IgG3, in analogy with IgM, uses the complement system for this function.
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Teresita
T
Díaz de Ståhl
Jörgen
J
Dahlstrom
Michael C
MC
Carroll
Birgitta
B
Heyman
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D001483:Base Sequence; D003165:Complement System Proteins / Q000502:physiology*; D017931:DNA Primers; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
D000941:Antigens; D017931:DNA Primers; D007074:Immunoglobulin G; D003165:Complement System Proteins