title: IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors.
abstract: Antigen-specific IgG antibodies, passively administered to mice or humans together with large particulate antigens like erythrocytes, can completely suppress the antibody response against the antigen. This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally. The mechanisms by which IgG suppresses antibody responses are poorly understood. We have here addressed whether complement or Fc-receptors for IgG (FcγRs) are required for IgG-mediated suppression. IgG, specific for sheep red blood cells (SRBC), was administered to mice together with SRBC and the antibody responses analyzed. IgG was able to suppress early IgM- as well as longterm IgG-responses in wildtype mice equally well as in mice lacking FcγRIIB (FcγRIIB knockout mice) or FcγRI, III, and IV (FcRγ knockout mice). Moreover, IgG was able to suppress early IgM responses equally well in mice lacking C1q (C1qA knockout mice), C3 (C3 knockout mice), or complement receptors 1 and 2 (Cr2 knockout mice) as in wildtype mice. Owing to the previously described severely impaired IgG responses in the complement deficient mice, it was difficult to assess whether passively administered IgG further decreased their IgG response. In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Joakim J E
authors.initials: JJ
authors.lastname: Bergström
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Heyman
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015922:Complement C1q / Q000172:deficiency*; D003176:Complement C3 / Q000172:deficiency*; D017707:Erythrocyte Transfusion; D055786:Gene Knockout Techniques; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007075:Immunoglobulin M / Q000378:metabolism; D051379:Mice; D011951:Receptors, Complement / Q000172:deficiency*; D017452:Receptors, IgG / Q000378:metabolism*; D012756:Sheep / Q000097:blood* / Q000276:immunology
chemical_list: D003176:Complement C3; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011951:Receptors, Complement; D017452:Receptors, IgG; D015922:Complement C1q