Disclosed herein are methods, reagents, and pharmaceutical compositions for modulating immune effector cell activation that does not requirean antigen-specific antibody. The IgG Fc region is shown herein to contain both a domain that binds an FcgammaR on immune effector cells and a non-overlapping region or domain that can bind Fc binding proteins on target cells, and that it is capable of bridging immune effector cells and target cells expressing Fc binding proteins without use of the antigen-binding region (Fab) of the antibody. Therefore, also disclosed are methods of enhancing or inhibiting passive ADCC in subjects.