RETRACTED: The IL-15Rα chain signals through association with Syk in human B cells (Retracted article. See vol. 186, pg. 2681, 2011)

The alpha -chain of the IL-15R (IL-15R alpha) serves as the specific, high-affinity receptor for IL-15. It is expressed by lymphoid and nonlymphoid cells, including B cell lymphoma lines. In this study, we have further explored IL-15R alpha -mediated signaling in activated primary B cells and in Raji cells, a human B-lymphoblastoid cell line which expresses the IL-15R alpha and IL-2R gamma chains, but lacks the IL-2R beta chain. Stimulation of Raji cells with IL-15 induces their proliferation and rescues them from C2-ceramide-induced apoptosis. By immunoprecipitation and Western blotting, we show that treatment of Raji cells and activated primary B cells with IL-15 induces coprecipitation of Syk kinase with the IL-15R alpha chain. Upon association, the activated Syk kinase phosphorylates the IL-15R alpha chain as well as phospholipase C gamma, which coprecipitates with Syk. Furthermore, transfection of Raji cells with stem-loop Syk antisense oligonucleotides prevents IL-15R alpha and phospholipase C gamma phosphorylation as well as the inhibition of apoptosis by IL-15. Mutation of a defined region of the intracellular signaling portion of IL-15R alpha (Tyr(227)) abrogates both the IL-15R alpha /Syk association and IL-15R alpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15R alpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells.