Efficient IgG-mediated suppression of primary antibody responses in Fcgamma receptor-deficient mice.
IgG antibodies can suppress more than 99% of the antibody response against the antigen to which they bind. This is used clinically to prevent rhesus-negative (Rh-) women from becoming immunized against Rh+ erythrocytes from their fetuses. The suppressive mechanism is poorly understood, but it has been proposed that IgG/erythrocyte complexes bind to the inhibitory Fc receptor for IgG (FcgammaRIIB) on the B cell surface, thereby triggering negative signals that turn off the B cell. We show that IgG induces the same degree of suppression of the response to sheep erythrocytes in animals lacking the known IgG-binding receptors FcgammaRIIB, FcgammaRI + III, FcgammaRI + IIB + III, and FcRn (the neonatal Fc receptor) as in wild-type animals. Reinvestigation of the ability of F(ab')2 fragments to suppress antibody responses demonstrated that they were nearly as efficient as intact IgG. In addition, monoclonal IgE also was shown to be suppressive. These findings suggest that IgG inhibits antibody responses through Fc-independent mechanisms, most likely by masking of antigenic epitopes, thereby preventing B cells from binding and responding to antigen. In agreement with this, we show that T cell priming is not abolished by passively administered IgG. The results have implications for the understanding of in vivo regulation of antibody responses and Rh prophylaxis.
Department of Genetics and Pathology, Unit of Pathology, Uppsala University, S-751 85 Uppsala, Sweden.
M C
MC
Karlsson
S
S
Wernersson
T
T
Diaz de Ståhl
S
S
Gustavsson
B
B
Heyman
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005333:Fetus; D006736:Horses; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007165:Immunosuppression Therapy; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012204:Rh-Hr Blood-Group System / Q000276:immunology; D012756:Sheep
D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System