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The Journal of Immunology, 2004, 173: 6676-6683.
Copyright © 2004 by The American Association of Immunologists

Follicular Dendritic Cells Produce IL-15 That Enhances Germinal Center B Cell Proliferation in Membrane-Bound Form1

Chan-Sik Park*, Sun-Ok Yoon*, Richard J. Armitage2,{dagger} and Yong Sung Choi3,*

* Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA 70121; and {dagger} Amgen, Seattle, WA 98119

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-15R{alpha} 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-2/15R{beta}{gamma}), but not a receptor for binding of soluble IL-15 (IL-15R{alpha}), 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.




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