IgE Synthesis in the Asthmatic Airway

The first signal is supplied by the activity of cytokines, IL-4/IL-13 these molecules are responsible for determining isotype specificity, i.e., immunoglobulin gene transcription at a specific region of the Ig locus in B cells (185,186). The 

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Substantial evidence has supported the role of IL-4 and IL-13 in the induction of IgE synthesis (194). Interleukin-4 and IL-13 are the only cytokines known that can induce IgE synthesis in vitro using the recombinant proteins (186,195). The role of IL-4 was initially identified in vitro, T-cell-derived IL-4 was able to induce IgE production by lipopolysaccharide (LPS)-stimulated murine B cells (196), and anti-IL-4/IL-4 receptor (IL-4R) antibodies inhibited IgE responses in experimental animals (197,198). The role of IL-4 in human IgE isotype switch in B cells from IgM to IgE has been established using normal unfractionated peripheral blood mononuclear cells (PBMCs) (199) and single B cells stimulated with murine and human T-cell clones (192,200). Interleukin-4 is produced by activated Th2-type CD4+ cells and Tc2 type CD8+ cells (201), mast cells, and basophils (202). Functions attributable to IL-4 include upregulation of surface CD23, MHC class II and IL-4 receptor expression on monocytes and B cells, and increased expression of VCAM-1 on endothelial cells. 

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