Molecular regulation of human IgE synthesis.
Understanding the induction and regulation of IgE synthesis in human B cells is crucial to elucidate the molecular pathogenesis of IgE-dependent diseases. Experimental data, in part supported by clinical observations, suggests that IgE regulation is a complex process involving several cellular and molecular interactions. A two-signal model is accepted for the induction of IgE synthesis in human B cells. The first signal is provided by the cytokines interleukin 4 or 13, which are secreted by T cells, mast cells, and basophils. The second signal for the induction of IgE synthesis requires cell contact between T and B cells. Engagement of the B cell antigen CD40 by the CD40 ligand (CD40L) expressed on T cells leads to subsequent isotype switching during immunoglobulin synthesis in B cells. The CD40-CD40L interaction is well established as a key signal for the induction of isotype switching while the elucidation of the role of other cell-cell interactions, for example, through adhesion molecules, needs further study. An important counteracting cytokine for IgE synthesis is interferon (IFN) gamma which is produced mainly by T lymphocytes. Several cell-contact molecules, cytokines, and various hormones have been shown to modulate IgE synthesis in vitro, suggesting a complex network of molecular events to be involved in the production of IgE. However, the relevance of these factors for IgE production in vivo requires further elucidation. Here we describe the molecular mechanisms known to be involved in the induction and regulation of human IgE synthesis and discuss the role of various molecules during this process. Furthermore, evidence is presented that the understanding of IgE synthesis provides a potential key for new therapeutic strategies in patients with IgE mediated diseases including atopic dermatitis.
Worm
M
M
Department of Dermatology, Charité-Virchow Klinikum, Humboldt University, Berlin, Germany.
Henz
B M
BM
D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand; D006801:Humans; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology; D010950:Plasma Cells / Q000378:metabolism*
D019013:CD40 Antigens; D018793:Interleukin-13; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E