Association of the interleukin-4 receptor alpha chain with p47(phox), an activator of the phagocyte NADPH oxidase in B cells

Interleukin (IL)-4 plays an important role in IgE synthesis in B cells and in Th2 differentiation in T cells. IL-4 conducts its biological activities through binding to the IL-4 receptor (IL-4R) on the surface of target cells . IL-4R are thought to be composed of the IL-4R a chain (IL-4R alpha) and e ither the IL-2R gamma chain or the IL-13R cc chain. We have previously show n that the membrane-proximal portion in the cytoplasmic domain of the human IL-4R alpha (hIL-4R alpha) is critical for proliferation, generation of ge rmline epsilon transcript, and activation of STAT6, based on analyses of tr uncated hIL4R alpha s. In this study, we found that p47(phox), an activator of the phagocyte NADPH oxidase, binds to this portion by the two-hybrid sy stem. Furthermore, we observed the association of p47(phox) with the hIL-4R alpha in B cells derived from a normal donor. These results suggest that p 47(phox) is involved in the signal transduction of IL-4 in B cells. However , activation of STAT6, CD23 expression, and IgE synthesis induced by IL-4 w ere not affected in p47(phox)-deficient patients, which raises the possibil ity that p47(phox) may be important in other signaling activities as well i n B cells. (C) 1999 Elsevier Science Ltd. All rights reserved.