Antibody-mediated regulation of the immune response.
Antibodies administered in vivo together with the antigen they are specific for can regulate the immune response to that antigen. This phenomenon is called antibody-mediated feedback regulation and has been known for over 100 years. Both passively administered and actively produced antibodies exert immunoregulatory functions. Feedback regulation can be either positive or negative, resulting in >1000-fold enhancement or >99% suppression of the specific antibody response. Usually, the response to the entire antigen is up- or downregulated, regardless of which epitope the regulating antibody recognizes. IgG of all isotypes can suppress responses to large particulate antigens like erythrocytes, a phenomenon used clinically in Rhesus prophylaxis. IgG suppression works in mice lacking the known Fc-gamma receptors (FcgammaR) and a likely mechanism of action is epitope masking. IgG1, IgG2a and IgG2b administered together with soluble protein antigens will enhance antibody and CD4+ T-cell responses via activating FcgammaR, probably via increased antigen presentation by dendritic cells. IgG3 as well as IgM also enhance antibody responses but their effects are dependent on their ability to activate complement. A possible mechanism is increased B-cell activation caused by immune complexes co-crosslinking the B-cell receptor with the complement-receptor 2/CD19 receptor complex, known to lower the threshold for B-cell activation. IgE-antibodies enhance antibody and CD4+ T-cell responses to small soluble proteins. This effect is entirely dependent on the low-affinity receptor for IgE, CD23, the mechanism probably being increased antigen presentation by CD23+ B cells.
Hjelm
F
F
Department of Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.
Carlsson
F
F
Getahun
A
A
Heyman
B
B
D000818:Animals; D000917:Antibody Formation; D025461:Feedback, Physiological; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D018448:Models, Immunological
D007074:Immunoglobulin G; D007075:Immunoglobulin M