Down regulation of Fc receptors by IVIgG

IVIgG preparations are now widely applied for immune modulatory treatment in various forms of autoimmune and immune complex diseases. Several controlled studies clearly demonstrated the clinical efficacy of this type of treatment; the underlying pathophysiological mechanisms, however, have yet to be elucidated. Among the mechanisms suggested to play a role in this context is the interaction of gamma globulin with Fc gamma receptors (Fc gamma R) expressed in the membrane of immunocompetent cells. Our studies concentrated on these aspects and focused on possible functional consequences of IgG-Fc gamma R interaction. By using the peripheral blood monocyte as a model system for an Fc gamma R-bearing cell, we confirmed previous reports by showing differences in Fc gamma R binding and Fc gamma R modulation induced by IgG in its various forms (monomeric IgG, Polymeric IgG, immune complexes). As biological consequences of Fc gamma R modulation, changes in effector and accessory function of these cells were observed. The results presented in this brief review emphasize especially the difference between ligand-oriented Fc gamma R diffusion (induced by surface-bound IgG) and true long-term down-modulation of Fc gamma R (mediated by fluid-phase IgG polymers) and show that only the down-modulation of Fc gamma R correlated with impaired functions of the affected cell.