Antibody feedback suppression: towards a unifying concept?
IgG antibodies can negatively regulate antibody responses. When IgG anti-sheep erythrocytes (SRBC) is administered to an animal together with SRBC, the response against SRBC will frequently be less than 1% of the response in animals immunized with SRBC alone. The mechanism behind this phenomenon is not fully understood. It has been suggested that suppression is caused by masking of epitopes by IgG, thus preventing B cells from recognizing the antigen. Other possible explanations are that IgG/antigen complexes are eliminated via Fc-receptor dependent phagocytosis or that the complexes inhibit B cell activation by co-crosslinking the B cell receptor for antigen and the inhibitory Fc-receptor, FcgammaRIIB, expressed by B cells. Whereas the first mechanism would operate independently of the Fc-portion of IgG, the two latter would be Fc-dependent. In the literature data has been presented supporting both Fc-dependence and Fc-independence of suppression. It has recently been shown that IgG suppresses more than 90% of the antibody response in gene targeted mice lacking the known Fc-receptors for IgG and that F(ab')2 fragments as well as IgE are efficient suppressors. These findings strongly suggest that IgG is able to efficiently suppress antibody responses independently of the Fc-part and favor the model of epitope masking. Here, a way of interpreting available experimental data which can explain many of the discrepancies in the literature, is presented.
Department of Genetics and Pathology, Uppsala University, Sweden. birgitta.heyman@patologi.uu.se
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Heyman
D000818:Animals; D015536:Down-Regulation / Q000276:immunology*; D005246:Feedback / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents