Learning objectives: Type I hypersensitivity reactions uniquely involve the IgE class of immunoglobulins (Ig). IgE differs from other classes of Ig in that the majority of the antibodies are bound to high affinity IgE FCεRs that are expressed on a variety of cell types. Some of these cell types, most notably, mast cells and basophils, are triggered to undergo rapid activation, degranulation, and release of bioactive mediators following binding of antigen to FCεRI-bound IgE. Because of the central role that IgE antibodies and these mediators play in the tissue injury typical of type I hypersensitivity, this article will review the various stages of B lymphocyte development, activation, and differentiation and comment, where appropriate on potential sites of deregulation in allergic disease. Data sources: A literature search of the stages of B lymphocyte differentiation with emphasis on events that concern IgE expression was performed. Results: B lymphocyte differentiation into IgE expressing cells is dependent upon three types of signals. The first signal is delivered through the B cell antigen receptor and is pivotal in determining the antigenic specificity of the response. The second signal is provided primarily by cytokines derived from T helper 2 (TH2) cells, ie, interleukin (IL)-4 and IL-13. These cytokines are under tight regulation and their role appears to be the stimulation of transcription through the Ig constant region genes. Finally, the third signal is provided via the interaction between the constitutively expressed CD40 molecule on B lymphocytes and CD154 (CD40 ligand), a molecule expressed on T lymphocytes following activation. Elevated levels of IgE in atopic individuals may result from the preferential activation of TH2 cells. Conclusions: A greater understanding of the regulation of IgE expression may be central to the development of more effective immunotherapy strategies designed to attenuate IgE synthesis.
|Original language||English (US)|
|Journal||Annals of Allergy, Asthma and Immunology|
|State||Published - Apr 2000|
ASJC Scopus subject areas
- Immunology and Allergy
- Pulmonary and Respiratory Medicine