Trapping of naive lymphocytes triggers rapid growth and remodeling of the fibroblast network in reactive murine lymph nodes

Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):E109-18. doi: 10.1073/pnas.1312585111. Epub 2013 Dec 23.


Adaptive immunity is initiated in T-cell zones of secondary lymphoid organs. These zones are organized in a rigid 3D network of fibroblastic reticular cells (FRCs) that are a rich cytokine source. In response to lymph-borne antigens, draining lymph nodes (LNs) expand several folds in size, but the fate and role of the FRC network during immune response is not fully understood. Here we show that T-cell responses are accompanied by the rapid activation and growth of FRCs, leading to an expanded but similarly organized network of T-zone FRCs that maintains its vital function for lymphocyte trafficking and survival. In addition, new FRC-rich environments were observed in the expanded medullary cords. FRCs are activated within hours after the onset of inflammation in the periphery. Surprisingly, FRC expansion depends mainly on trapping of naïve lymphocytes that is induced by both migratory and resident dendritic cells. Inflammatory signals are not required as homeostatic T-cell proliferation was sufficient to trigger FRC expansion. Activated lymphocytes are also dispensable for this process, but can enhance the later growth phase. Thus, this study documents the surprising plasticity as well as the complex regulation of FRC networks allowing the rapid LN hyperplasia that is critical for mounting efficient adaptive immunity.

Keywords: MyD88; fibroblasts; lymph node swelling; lymphotoxin; stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cell Movement
  • Cell Proliferation
  • Dendritic Cells / cytology
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Homeostasis
  • Inflammation
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism*
  • Lymphocyte Activation
  • Lymphocytes / cytology*
  • Lymphotoxin-alpha / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence / methods
  • Myeloid Differentiation Factor 88 / metabolism
  • Stromal Cells / cytology
  • T-Lymphocytes / cytology


  • Lymphotoxin-alpha
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88