Feedback regulation by IgG antibodies

Antibodies of all classes and subclasses except IgD have been shown to have the capacity to feedback regulate the production of themselves. This phenomenon has been known for over a century and was originally described by the first Nobel laureate in physiology, Emil von Behring. When an animal is immunized with antibodies together with an antigen they recognize, the antibody response to this very antigen is often dramatically modulated. Sometimes feedback regulation results in complete suppression and sometimes in several 100-fold enhancement of the specific response. An immune complex contains the antigen, the specific antibodies bound to it and, when the antibodies can activate complement, complement factors, and can, therefore, bind to antigen-specific receptors on B cells (BCR), various Fc-receptors (FcRs) as well as to complement receptors. This gives the immune complex many possibilities to regulate the immune response via e.g. receptor cocrosslinking, leading to changes in signal transduction, or by increased antigen uptake and processing by antigen-presenting cells. This review will focus on the role of IgG as a feedback regulator. Three different pathways will be discussed: (i) the ability of IgG to induce complete suppression of erythrocyte responses, which takes place equally efficiently in the absence as in the presence of FcgammaRs, (ii) the ability of IgG to enhance responses to soluble protein antigens, a phenomenon severely impaired in FcRgamma-chain-deficient mice (with non-functional FcgammaRI and FcgammaRIII), and (iii) the ability of IgG to, via FcgammaRIIB, downregulate the response to IgG-complexed soluble antigens.