IL-4Rα-Expressing B Cells Are Required for CXCL13 Production by Fibroblastic Reticular Cells

Lalit Kumar Dubey, Burkhard Ludewig, Sanjiv A. Luther, Nicola L. Harris

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Adaptive type 2 immune responses against the intestinal helminth Heligmosomoides polygyrus (Hp) require the interaction of follicle-associated CXCR5 + dendritic cells with naive T cells in the draining mesenteric lymph nodes (mLNs). However, the source of CXCL13 responsible for attracting CXCR5 + dendritic cells has remained unclear. Using multiplex imaging combined with deep tissue analysis, we observed new CXCL13 + fibroblastic reticular cells surrounding paracortical and cortical B cell follicles in the mLNs of infected mice. CXCL13 + fibroblasts expressed markers of marginal reticular cells (MRCs), and their expansion required lymphotoxin (LT)-dependent interactions between IL-4Rα-expressing B cells and CCL19 + fibroblasts. Infection-induced follicles did not necessarily contain follicular dendritic cells (FDCs), indicating that CXCL13 + fibroblasts may instead drive their formation. These data reveal a role for lymphotoxin signaling to CCL19 + fibroblasts in the development of CXCL13 + MRC-like cells and adaptive type 2 immunity in response to helminth infection. MRCs are a specialized, CXCL13-producing, stromal population located beneath the subcapsular sinus of lymph nodes. Dubey et al. demonstrate that intestinal helminth infection drives the remodeling and development of MRCs toward the paracortical region within the draining mLNs and requires the expression of type 2 cytokines and intimate B cell-stromal cell interactions.

Original languageEnglish
Pages (from-to)2442-2458.e5
Number of pages22
JournalCell Reports
Volume27
Issue number8
DOIs
Publication statusPublished - 21 May 2019

Keywords

  • CXCL13
  • fibroblastic reticular cells
  • Heligmosomoides polygyrus
  • helminth infection
  • IL-4Rα
  • interfollicular region
  • intestinal infection
  • MAdCAM-1
  • marginal reticular cells
  • mesenteric lymph node

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