The IL-15Rα chain signals through association with Syk in human B cells

E. Bulanova, V. Budagian, T. Pohl, H. Krause, H. Dürkop, Ralf Paus, S. Bulfone-Paus

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The α-chain of the IL-15R (IL-15Rα) 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-15Rα-mediated signaling in activated primary B cells and in Raji cells, a human B-lymphoblastoid cell line which expresses the IL-15Rα and IL-2Rγ chains, but lacks the IL-2Rβ 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-15Rα chain. Upon association, the activated Syk kinase phosphorylates the IL-15Rα chain as well as phospholipase Cγ, which coprecipitates with Syk. Furthermore, transfection of Raji cells with stem-loop Syk antisense oligonucleotides prevents IL-15Rα and phospholipase Cγ phosphorylation as well as the inhibition of apoptosis by IL-15. Mutation of a defined region of the intracellular signaling portion of IL-15Rα (Tyr227) abrogates both the IL-15Rα/Syk association and IL-15Rα phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Rα 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.

Original languageEnglish (US)
Pages (from-to)6292-6302
Number of pages11
JournalJournal of Immunology
Volume167
Issue number11
StatePublished - Dec 1 2001
Externally publishedYes

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Interleukin-15
B-Lymphocytes
Type C Phospholipases
Interleukin-15 Receptors
Phosphorylation
Apoptosis
Cell Line
Antisense Oligonucleotides
B-Cell Lymphoma
Immunoprecipitation
Interleukin-2
Transfection
Signal Transduction
Stem Cells
Western Blotting
Lymphocytes
Mutation
Syk Kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Bulanova, E., Budagian, V., Pohl, T., Krause, H., Dürkop, H., Paus, R., & Bulfone-Paus, S. (2001). The IL-15Rα chain signals through association with Syk in human B cells. Journal of Immunology, 167(11), 6292-6302.

The IL-15Rα chain signals through association with Syk in human B cells. / Bulanova, E.; Budagian, V.; Pohl, T.; Krause, H.; Dürkop, H.; Paus, Ralf; Bulfone-Paus, S.

In: Journal of Immunology, Vol. 167, No. 11, 01.12.2001, p. 6292-6302.

Research output: Contribution to journalArticle

Bulanova, E, Budagian, V, Pohl, T, Krause, H, Dürkop, H, Paus, R & Bulfone-Paus, S 2001, 'The IL-15Rα chain signals through association with Syk in human B cells', Journal of Immunology, vol. 167, no. 11, pp. 6292-6302.
Bulanova E, Budagian V, Pohl T, Krause H, Dürkop H, Paus R et al. The IL-15Rα chain signals through association with Syk in human B cells. Journal of Immunology. 2001 Dec 1;167(11):6292-6302.
Bulanova, E. ; Budagian, V. ; Pohl, T. ; Krause, H. ; Dürkop, H. ; Paus, Ralf ; Bulfone-Paus, S. / The IL-15Rα chain signals through association with Syk in human B cells. In: Journal of Immunology. 2001 ; Vol. 167, No. 11. pp. 6292-6302.
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