The IL-15Rα Chain Signals Through Association with Syk in Human B Cells

Bulanova, Elena; Budagian, Vadim; Pohl, Thomas; Krause, Hans; Dürkop, Horst; Paus, Ralf; Bulfone–Paus∥, Silvia

doi:10.4049/jimmunol.167.11.6292

Cited by 78 publications

(66 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, the detected STAT6 protein was 65 kDa in size, corresponding to the earlier reported C-terminal truncated isoform predominantly found in mast cells (42). IL-15 also induced the phosphorylation of JAK2 and Syk, and association of Syk with IL-15R␣, which is in agreement with the previous findings (14,28). Recent studies have also underlined the involvement of the ␥ c chain and JAK3 in activation, proliferation, and survival of mast cells (48 -50).…”

Section: Discussionsupporting

confidence: 80%

“…In fact, the property of IL-15 to substitute the growth-promoting effect of IL-3 of the genetically engineered BA/F3 cells, diminishing the number of apoptotic cells and resulting in survival of 80 -90% of the cells, appears to be in accordance with its well-documented antiapoptotic function (10,27,28).…”

Section: Discussionmentioning

confidence: 76%

“…We have recently shown that Syk kinase associates with the intracellular part of IL-15R␣ and becomes phosphorylated and activated upon IL-15 treatment in lymphoid cells (28). To prove the involvement of Syk in IL-15-mediated signaling in mast cells, BMMCs were stimulated for 15 min with IL-15.…”

Section: Il-15 Induces the Phosphorylation Of Syk Kinase Which Assocmentioning

confidence: 99%

“…It has been assumed that the IL-15R␣ chain, like IL-2R␣, is not capable of signaling when it is expressed in the absence of IL-2R␤ or ␥ c (8,18,19). However, we have recently shown that IL-15 can rescue murine fibroblasts from TNF-␣-induced apoptosis by recruitment of TNFR-associated factor 2 to the IL-15R␣ chain (27), and that IL-15R␣-mediated signaling in the human B cell line Raji occurs through association of IL-15R␣ chain with Syk (28).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Mast Cells Express Novel Functional IL-15 Receptor α Isoforms

Bulanova

Budagian

Orinska

et al. 2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Mast cells previously have been reported to be regulated by IL-15 and to express a distinct IL-15R, termed IL-15RX. To further examine IL-15 binding and signaling in mast cells, we have studied the nature of the IL-15R and some of its biological activities in these cells. In this study, we report the existence of three novel isoforms of the IL-15Rα chain in murine bone marrow-derived mast cells as a result of an alternative exon-splicing mechanism within the IL-15Rα gene. These correspond to new mRNA transcripts lacking exon 4; exons 3 and 4; or exons 3, 4, and 5 (IL-15RαΔ4, IL-15RαΔ3,4, IL-15RαΔ3,4,5). After transient transfection in COS-7 cells, all IL-15Rα isoforms associate with the Golgi apparatus, the endoplasmic reticulum, the perinuclear space, and the cell membrane. Analysis of glycosylation pattern demonstrates the usage of a single N-glycosylation site, while no O-glycosylation is observed. Importantly, IL-15 binds with high affinity to, and promotes the survival of, murine BA/F3 cells stably transfected with the IL-15Rα isoforms. Furthermore, we report that signaling mediated by IL-15 binding to the newly identified IL-15Rα isoforms involves the phosphorylation of STAT3, STAT5, STAT6, Janus kinase 2, and Syk kinase. Taken together, our data indicate that murine mast cells express novel, fully functional IL-15Rα isoforms, which can explain the selective regulatory effects of IL-15 on these cells.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 76%

Section: Il-15 Induces the Phosphorylation Of Syk Kinase Which Assocmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Mast Cells Express Novel Functional IL-15 Receptor α Isoforms

Bulanova

Budagian

Orinska

et al. 2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The specific binding to IL-15 is conferred by IL-15R␣ to deliver IL-15 signal (35), or via direct cell-cell contact as a membrane-bound ligand (40,41). Although IL-15 stimulates T and NK cells, IL-15 also plays important functions in B cells and malignancies of B cell origin (42)(43)(44)(45)(46)(47)(48). Moreover, IL-15 is produced by synoviocytes (49), which have intrinsic properties of FDCs (50).…”

mentioning

confidence: 99%

Follicular Dendritic Cells Produce IL-15 That Enhances Germinal Center B Cell Proliferation in Membrane-Bound Form

Park

Yoon

Armitage

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Factors that control the survival and proliferation of Ag-stimulated B cells within the germinal center (GC) are crucial for humoral immune responses with high affinity Abs against infectious agents. The follicular dendritic cell (FDC) is known as a key cellular component of the GC microenvironment for GC-B cell survival and proliferation. In this study, we report that IL-15 is produced by human FDC in vivo and by an FDC cell line, FDC/HK cells, in vitro. IL-15 is captured by IL-15Rα on the surface of FDC/HK cells. The surface IL-15 is functionally active and augments GC-B cell proliferation. Because GC-B cells have the signal-transducing components (IL-2/15Rβγ), but not a receptor for binding of soluble IL-15 (IL-15Rα), IL-15 signaling is possibly transduced by transpresentation from FDCs to GC-B cells via cell-cell contact. Together, these results suggest that IL-15 from FDC, in membrane-bound form, plays an important role in supporting GC-B cell proliferation, proposing a new target for immune modulation as well as treatment of B cell tumors of GC origin.

show abstract

Interleukin‐15 inhibits sodium nitroprusside–induced apoptosis of synovial fibroblasts and vascular endothelial cells

Yang¹,

Thornton²,

Grom³

2002

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. One of the pathologic hallmarks of juvenile rheumatoid arthritis (JRA) is a tumor-like expansion of inflamed synovial tissue, or pannus, which causes much of the joint damage in this disease. The expansion of pannus is supported by extensive formation of new blood vessels. We have previously shown that revascularization of minced JRA synovial tissues engrafted into SCID mice correlated with the intensity of inflammatory activity in the tissues and with interleukin-15 (IL-15) expression. Since synovial vascular endothelial cells (VECs) expressed IL-15 receptors, the present study was undertaken to investigate the hypothesis that IL-15 might play a role in neovascularization of the pannus.Methods. To evaluate IL-15 for possible angiogenic activity, we assessed the ability of recombinant human IL-15 (rHuIL-15) to induce VEC growth directly and to stimulate synovial cells to produce endothelial growth factors. Since IL-15 had been shown to inhibit apoptosis of certain immune cells, we were also interested in whether it might have similar effects on VECs. Apoptosis was induced by addition of sodium nitroprusside (SNP) at 1-2 mM to >80% confluent primary VECs, and numbers of apoptotic cells were determined by annexin V assay.Results. Addition of rHuIL-15 at 10-100 ng/ml to primary synovial fibroblast cultures failed to upregulate expression of vascular endothelial growth factor and angiopoietin 1 by these cells. Although rHuIL-15 failed to induce a mitogenic response of VECs, it promoted survival of these cells on Matrigel. Preincubation of VECs with rHuIL-15 at 50 ng/ml significantly reduced the proportion of VECs undergoing apoptosis.Conclusion. IL-15 promotes survival of VECs on Matrigel and inhibits SNP-induced apoptosis of endothelial cells. We hypothesize that this mechanism may be relevant to the stabilization of newly formed vascular structures in JRA synovium.

show abstract

The IL-15Rα Chain Signals Through Association with Syk in Human B Cells

Cited by 78 publications

References 72 publications

Mast Cells Express Novel Functional IL-15 Receptor α Isoforms

Mast Cells Express Novel Functional IL-15 Receptor α Isoforms

Follicular Dendritic Cells Produce IL-15 That Enhances Germinal Center B Cell Proliferation in Membrane-Bound Form

Interleukin‐15 inhibits sodium nitroprusside–induced apoptosis of synovial fibroblasts and vascular endothelial cells

Contact Info

Product

Resources

About