Multiple loss of effector cell functions in FcR gamma-deficient mice

Immunoglobulin Fc receptor (FcR) gamma subunit is a component of low affinity receptor for IgG, Fc gamma RIII, as well as high affinity receptor for IgE, Fc epsilon RI. This subunit is required for efficient surface expression of these FcRs on various cells in immune system. The FcR gamma-deficient mice, generated by gene targeting in embryonic stem cells, exhibit multiple defects in FcR-mediated effector cell responses, including absence of phagocytic activity against opsonized red blood cells by activated macrophages, loss of antibody-dependent cell-mediated cytotoxicity manifested by IL-2-induced splenic NK cells, and unresponsiveness of mast cells to crosslinking of IgE on these cells. These results demonstrate an indispensable role of FcR gamma for functional expression of FcRs, and clearly indicate the importance of Fc gamma RIII as well as Fc epsilon RI for these effector functions. Since FcR gamma-deficient mice is unable to mount the type II and type III hypersensitivity reactions, it is suggested that FcRs play pivotal roles in initiating these reaction cascades. The mutant mice should prove to be useful in evaluating FcRs in various humoral and cellular immune responses, and in developing new strategies for treatment of immunodeficiency as well as autoimmune disorders.