Regulation of B lymphocyte differentiation

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 Fc epsi lon Rs that are expressed on a variety of cell types. Some of these cell ty pes, most notably, mast cells and basophils, are triggered to undergo rapid activation, degranulation, and release of bioactive mediators following bi nding of antigen to Fc epsilon RI-bound IgE. Because of the central role th at IgE antibodies and these mediators play in the tissue injury typical of type I hypersensitivity, this article will review the Various stages of B l ymphocyte development, activation, and differentiation and comment, where a ppropriate on potential sites of deregulation in allergic disease. Data sources: A literature search of the stages of B lymphocyte differentia tion with emphasis on events that concern IgE expression was performed. Results: B lymphocyte differentiation into IgE expressing cells is dependen t upon three types of signals. The first signal is delivered through the B cell antigen receptor and is pivotal in determining the antigenic specifici ty of the response. The second signal is provided primarily by cytokines de rived 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 stimu lation of transcription through the Ig constant region genes. Finally, the third signal is provided via the interaction between the constitutively exp ressed CD40 molecule on B lymphocytes and CD154 (CD40 ligand), a molecule e xpressed on T lymphocytes following activation. Elevated levels of IgE in a topic individuals may result from the preferential activation of TH2 cells. Conclusions: A greater understanding of the regulation of IgE expression ma y be central to the development of more effective immunotherapy strategies designed to attenuate IgE synthesis.