Analysis of the Expression Mechanism of Immunoglobulin E by Interleukin-4

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(1) Interleukin-4 (IL-4) and IL-13 are functionally similar cytokines. The functional IL-4 receptor (IL-4R) consists of the IL-4Ralpha chain (IL-4Ralpha) and the IL-2Rgamma chain (gamma_c), which is shared by the IL-2, IL-7, IL-9, and IL-15 receptors. The functional IL-13R is thought to involve the IL-4Ralpha, but not gammac. In this study, we have analyzed activation of members of the Janus tyrosine kinase (Jak) family and signal transducers and activators of transcription (STAT) 6 induced by IL-4 and IL-13 in EBV-transformed B cells derived from two patients of X-linked severe combined immunodeficiency (XSCID), who have mutations of the gamma_c gene in the extracellular and intracellular domains. In these B cells, IL-4 failed to induce tyrosine phosphorylation of Jak3 and activation of STAT6, or activation of these molecules was significantly decreased compared with EBV-transformed normal B cells. In contrast, IL-13 activated STAT6 in thses cells as well as normal B cells. However, Jak3 was not activated by IL-13, even in normal B cells. These results clearly indicated that gamma_c is essential for activation of Jak3 and STAT6 in the signal transduction pathway of IL-4 in human B cells, and that IL-13 dose not utilize gamma_c but activates STAT6 through an alternative pathway, which is not impaired in B cells of XSCID patients.