Follicular dendritic cells produce IL-15 that enhances germinal center B cell proliferation in membrane-bound form.
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-15Ralpha 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-2/15Rbetagamma), but not a receptor for binding of soluble IL-15 (IL-15Ralpha), 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.
Park
Chan-Sik
CS
Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
Yoon
Sun-Ok
SO
Armitage
Richard J
RJ
Choi
Yong Sung
YS
D000276:Adjuvants, Immunologic / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism*; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000276:immunology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; C508024:IL15RA protein, human; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha