SIGNAL-TRANSDUCTION BY IMMUNOGLOBULIN FC-RECEPTORS

Receptors for the Fc portion of immunoglobulin molecules (FcR) present on leukocyte cell membranes mediate a large number of cellular respon ses that are very important in host defense. Cross-linking of FcR by i mmune complexes leads to functions such as phagocytosis, cell cytotoxi city, production and secretion of inflammatory mediators, and modulati on of the immune response, Molecular characterization of FcRs indicate s the existence of several types of these receptors, which seem to be redundant in their cell distribution and function, There is a great de al of interest in understanding how these various receptors signal the cell to respond in different ways during inflammation and the immune response. Previous studies indicate that FcR signaling shares elements with the T and B cell antigen receptors. Signaling is initiated in al l of them by activation of tyrosine kinases of the Src and ZAP-70 fami lies, Subsequent events, which vary depending on the cell type and rec eptor involved, include activation of other enzymes such as phospholip ase C gamma 1, phosphatidylinositol-3-kinase, and mitogen-activated pr otein kinase. Several recent lines of research, including studies of p hagocytosis by FcR-transfected cells, antibody-dependent cytotoxicity by natural killer cells, mast cell degranulation, and FcR-deficient mi ce,have given us new insights on the signal transduction pathways acti vated by FcRs, This review describes the advances in these areas and p resents a general model for FOR-mediated signaling.