Monomeric IgE and mast cell development, survival and function.

Mast cells play a major role in allergy and anaphylaxis, as well as a protective role in immunity against bacteria and venoms (innate immunity) and T-cell activation (acquired immunity).1,2 It was long thought that two steps are essential to mast cell activation. The first step (sensitization) occurs when antigen-specific IgE binds to its high-affinity IgE receptor (FcεRI) expressed on the surface of mast cells. The second step occurs when antigen (Ag) or anti-IgE binds antigen-specific IgE antibodies bound to FcεRI present on the mast cell surface (this mode of stimulation hereafter referred to as IgE+Ag or IgE+anti-IgE stimulation, respectively).Conventional wisdom has been that monomeric IgE plays only an initial, passive role in mast cell activation. However, recent findings have shown that IgE binding to its receptor FcεRI can mediate mast cell activation events even in the absence of antigen (this mode of stimulation hereafter referred to as IgE(-Ag) stimulation). Different subtypes of monomeric IgEs act via IgE(-Ag) stimulation to elicit varied effects on mast cells function, survival and differentiation. This chapter will describe the role of monomeric IgE molecules in allergic reaction, the various effects and mechanisms of action of IgE(-Ag) stimulation on mast cells and what possible developments may arise from this knowledge in the future. Since mast cells are involved in a variety of pathologic and protective responses, understanding the role that monomeric IgE plays in mast cell function, survival and differentiation will hopefully lead to better understanding and treatment of asthma and other allergic diseases, as well as improved understanding of host response to infections.