Follicular dendritic cells produce IL-15 that enhances germinal center B cell proliferation in membrane-bound form

J Immunol. 2004 Dec 1;173(11):6676-83. doi: 10.4049/jimmunol.173.11.6676.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / biosynthesis*
  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / physiology*
  • Apoptosis / immunology
  • B-Lymphocyte Subsets / cytology*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Cell Communication / immunology
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells, Follicular / immunology*
  • Dendritic Cells, Follicular / metabolism*
  • Germinal Center / cytology*
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Humans
  • Interleukin-15 / biosynthesis*
  • Interleukin-15 / metabolism
  • Interleukin-15 / physiology*
  • Protein Binding / immunology
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Interleukin-2 / physiology
  • Signal Transduction / immunology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Adjuvants, Immunologic
  • IL15RA protein, human
  • Interleukin-15
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha