Down Regulation of Fc Receptors by IVIgG

Abstract

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 γ globulin with Fcγ receptors (FcγR) expressed in the membrane of immunocompetent cells. Our studies concentrated on these aspects and focused on possible functional consequences of IgG-FcγR interaction. By using the peripheral blood monocytc as a model system for an FcγR-bearing cell, we confirmed previous reports by showing differences in FcγR binding and FcγR modulation induced by IgG in its various forms (monomeric IgG, polymeric IgG, immune complexes). As biological consequences of FcγR 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 FcγR diffusion (induced by surface-bound IgG) and true long-term down-modulation of FcγR (mediated by fluidphase IgG polymers) and show that only the down-modulation of FcγR correlated with impaired functions of the affected cell.

Key Words:

• Fcγ receptors
• interaction with IgG in its various forms
• Fcγ receptor modulation
• functional consequences
• human monocytes
• expression of FcγR in the membrane of
• human monocytes
• effects of FcγR modulation on effector and accessory function of
• IgG
• FcγR modulation by various forms of