FCR GAMMA-CHAIN DELETION RESULTS IN PLEIOTROPIC EFFECTOR CELL DEFECTS

The gamma subunit of immunoglobulin Fc receptors is an essential compo nent of the high-affinity receptor for IgE (Fc epsilon RI) and the low -affinity receptor for IgG (Fc gamma RIII) and is associated with the high-affinity receptor for IgG (Fc gamma RI) and the T cell receptor-C D3 complex. It is required for both receptor assembly and signal trans duction. Targeted disruption of this subunit results in immunocompromi sed mice. Activated macrophages from gamma chain-deficient mice unexpe ctedly lack the ability to phagocytose antibody-coated particles, desp ite normal binding. Defects in NK cell-mediated antibody-dependent cyt otoxicity and mast cell-mediated allergic responses are evident in the se animals, establishing the indispensable role of FcRs in these respo nses. However, loss of gamma chain does not appear to perturb T cell d evelopment, since both thymic and peripheral T cell populations appear normal. These mice thus represent an important tool for evaluating th e role of these receptors in humoral and cellular immune responses.