Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells

J Exp Med. 2014 Jun 2;211(6):1109-22. doi: 10.1084/jem.20132409. Epub 2014 May 26.

Abstract

Follicular dendritic cells (FDCs) regulate B cell function and development of high affinity antibody responses but little is known about their biology. FDCs associate in intricate cellular networks within secondary lymphoid organs. In vitro and ex vivo methods, therefore, allow only limited understanding of the genuine immunobiology of FDCs in their native habitat. Herein, we used various multicolor fate mapping systems to investigate the ontogeny and dynamics of lymph node (LN) FDCs in situ. We show that LN FDC networks arise from the clonal expansion and differentiation of marginal reticular cells (MRCs), a population of lymphoid stromal cells lining the LN subcapsular sinus. We further demonstrate that during an immune response, FDCs accumulate in germinal centers and that neither the recruitment of circulating progenitors nor the division of local mature FDCs significantly contributes to this accumulation. Rather, we provide evidence that newly generated FDCs also arise from the proliferation and differentiation of MRCs, thus unraveling a critical function of this poorly defined stromal cell population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Lineage / immunology*
  • Cell Proliferation
  • Dendritic Cells, Follicular / immunology*
  • Dendritic Cells, Follicular / metabolism
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Mesoderm / cytology
  • Mesoderm / immunology
  • Mesoderm / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • RANK Ligand / immunology
  • RANK Ligand / metabolism
  • Receptors, Complement 3b / immunology
  • Receptors, Complement 3b / metabolism
  • Receptors, Complement 3d / immunology
  • Receptors, Complement 3d / metabolism
  • Stem Cells / immunology
  • Stem Cells / metabolism
  • Stromal Cells / immunology
  • Stromal Cells / metabolism

Substances

  • Luminescent Proteins
  • RANK Ligand
  • Receptors, Complement 3b
  • Receptors, Complement 3d
  • Tnfsf11 protein, mouse