Fc receptors and feedback regulation by antibodies

Abstract: The purpose of this investigation was to determine the role of Fc receptors for IgG (FcγRI, FcγRIIB, FcγRIII and FcRn) in immunoregulation. IgG is known to enhance the response to soluble antigens such as bovine serum albumin whereas the response to particulate antigens is suppressed.The ability of IgG to induce specific suppression of immune responses has been used clinically to prevent haemolytic disease of the newborn (Rhesus prophylaxis). The favoured mechanism behind IgG-mediated suppression has been specific inhibition of antibody production through an inhibitory Fc receptor for IgG, FcγRIIB. We here study the importance of Fc receptors for IgG using Fc receptor-deficient mice immunised with sheep red blood cells alone or together with IgG anti-sheep red blood cells. IgG was able to suppress the primary response in all Fc receptor-deficient mice measured as number of sheep red blood cell specific B cells. In addition, IgE and F(ab')2 fragments of IgG induced antigen-specific suppression, suggesting an Fc-independent mechanism involving masking of epitopes. FcγRIIB was required for suppression of secondary antibody responses in vitro but not in vivo.To study the enhancing effect by IgG, the Fc receptor-deficient mice were immunised with haptenated bovine serum albumin alone or together with hapten-specific IgG. The resulting enhancement was measured as specific bovine serum albumin antibody in serum. We found that in order for IgG to enhance the response to soluble antigen there is a requirement for the common-y chain which is a part of FcγRI and FcγRIII. Using mice specifically deficient for FcγRIII we find that IgG can enhance the response pointing towards FcγRI as the receptor responsible for the effect. An additional finding was that theenhancement was greatly elevated in mice lacking FcγRIIB. This suggests that FcγRIIB has a function in preventing antibody responses from exceeding a certain level rather than in causing complete suppression.

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