Ontogeny of stromal organizer cells during lymph node development

Cécile Bénézech, Andrea White, Emma Mader, Karine Serre, Sonia Parnell, Klaus Pfeffer, Carl F Ware, Graham Anderson, Jorge H Caamaño

Research output: Contribution to journalArticlepeer-review

Abstract

The development of secondary lymphoid organs, such as lymph nodes (LNs), in the embryo results from the reciprocal action between lymphoid tissue inducer (LTi) cells and stromal cells. However, the initial events inducing LN anlagen formation before the LTi stromal cells cross-talk interactions take place are not fully elucidated. In this study, we show that the inguinal LN anlagen in mouse embryos developed from mesenchymal cells surrounding the lymph sacs, spherical structures of endothelial cells that bud from veins. Using inguinal and mesenteric LNs (mLNs), we provide evidence supporting a two-step maturation model for stromal cells: first, ICAM-1(-)VCAM-1(-) mesenchymal precursor cells become ICAM-1(int)VCAM-1(int) cells, in a process independent of LTi cells and lymphotoxin beta receptor (LTbetaR) signaling. The second step involves the maturation of ICAM-1(int)VCAM-1(int) cells to ICAM-1(high)VCAM-1(high) mucosal addressin cell adhesion molecule-1(+) organizer cells and depends on both LTi cells and LTbetaR. Addition of alphaLTbetaR agonist to LN organ cultures was sufficient to induce ICAM-1(int)VCAM-1(int) cells to mature. In LtbetaR(-/-) embryos, both inguinal and mLN stromal cells showed a block at the ICAM-1(int)VCAM-1(int) stage, and, contrary to inguinal LNs, mLNs persist longer and contained LTi cells, which correlated with the sustained gene expression of Il-7, Cxcl13, and, to a lesser degree, Ccl21. Taken together, these results highlight the importance of the signals and cellular interactions that induce the maturation of stromal cells and ultimately lead to the formation of lymphoid tissues.
Original languageEnglish
Pages (from-to)4521-30
Number of pages10
JournalJournal of Immunology
Volume184
Issue number8
DOIs
Publication statusPublished - 15 Apr 2010

Keywords

  • Animals
  • B-Lymphocyte Subsets
  • Cell Differentiation
  • Endothelium, Lymphatic
  • Immunophenotyping
  • Lymph Nodes
  • Mesenchymal Stromal Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Culture Techniques
  • Stromal Cells
  • T-Lymphocyte Subsets

Fingerprint

Dive into the research topics of 'Ontogeny of stromal organizer cells during lymph node development'. Together they form a unique fingerprint.

Cite this