The quantity and duration of FcR signals determine mast cell degranulation and survival

Immunoglobulin E (IgE) bound to multivalent antigen (Ag) elicits mast cell degranulation but not survival; on the contrary, IgE in the absence of Ag (IgE(-Ag)) induces survival only but not degranulation. Although these distinct responses are mediated through the same receptor, Fc RI, the molecular mechanism generating the divergence is largely unknown. We recently showed that the signals through FcR chain are essential for IgE(-Ag)–induced mast cell survival as well as IgE( Ag)–induced degranulation. To determine whether the cellular output is regulated by the quantity of FcR signal, we expressed CD8/FcR chimeras (CD8/ ) in bone marrow–derived mast cells (BMMCs) from FcR / mice to manipulate the strength of FcR signals by anti-CD8 cross-linking. Cross-linking of CD8/ induced mast cell survival and degranulation. Survival was induced by weaker stimulation than needed for degranulation in terms of anti-CD8 concentration and the valency of chimera. However, sustained extracellular signalregulated kinase (Erk) activation seems to regulate survival even when the activation signal was strong enough to elicit degranulation. Generation of sustained Erk activation by active mitogen-activated protein kinase kinase (MEK) induced BMMC survival. These results suggest that the duration and the magnitude of FcR signals may determine mast cell survival and degranulation, respectively. (Blood. 2004;103:3093-3101)