Hibbert, Linda Margaret; (1996) Structure and function of IL-4 and IL-13 receptors on human B cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

IL-4 and IL-13 are structurally related cytokines with overlapping biological properties on human B lymphocytes. The IL-4 receptor is composed of a 140KDa ? chain (IL-α) and the common ? chain (? c). Receptor binding studies indicate a shared component for the IL-4 and IL-13 receptors. Initial experiments compared effects of IL-4 and IL-13 on human tonsillar B cells in functional assays. The major difference between the two cytokines was that the magnitude of the response to IL-4 was much greater than the response to IL-13. The common receptor components were further investigated using antibodies to the IL-4 receptor, which could inhibit both IL-4 and IL-13 responses. In addition the effects of mutant IL-4 molecules on responses to IL-4 and IL-13 was studied. These mutants are potent inhibitors of IL-4 responses and some but not all of the mutants could also inhibit IL-13 responses. The studies suggest that IL-4 and IL-13 share a common receptor, probably composed of the IL-α chain and an IL-13 binding chain. Binding of both cytokines to the IL-α receptor chain has also been investigated using a BIAcore™ biosensor. IL-4 was found to bind with high affinity but no significant binding of IL-13 was observed. Overlapping function of IL-4 and IL-13 was also studied by looking at second messenger generation in response to the cytokines. It was confirmed that IL-4 signalled through a novel pathway involving a transient increase in IP3 and calcium followed by sustained increases in cAMP. This signalling pathway was also activated in human B cells by IL-13. Various intracellular proteins were also phosphorylated on tyrosine in response to IL-4 and IL-13 but the patterns obtained were not identical. The results obtained have enabled us to construct a model for a receptor shared between IL-4 and IL-13, consisting of the IL-α chain and an IL-13 binding chain.

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