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Chain Signals Through Association with Syk in Human B Cells1
*
Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany; Departments of
Urology and
Pathology, University Hospital Benjamin Franklin, Free University, Berlin, Germany; and
Department of Dermatology, University Hospital Eppendorf, University of Hamburg, Hamburg, Germany
The 
-chain of the IL-15R (IL-15R) 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-mediated signaling in activated primary
B cells and in Raji cells, a human B-lymphoblastoid cell line which
expresses the IL-15R and IL-2R
chains, but lacks the IL-2R
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 chain. Upon
association, the activated Syk kinase phosphorylates the IL-15R
chain as well as phospholipase C, which coprecipitates with Syk.
Furthermore, transfection of Raji cells with stem-loop Syk antisense
oligonucleotides prevents IL-15R and phospholipase C
phosphorylation as well as the inhibition of apoptosis by IL-15.
Mutation of a defined region of the intracellular signaling portion of
IL-15R (Tyr227) abrogates both the IL-15R/Syk
association and IL-15R phosphorylation. Taken together, this
suggests that Syk kinase physically and functionally associates with
the IL-15R 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.
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