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

Cell Rep. 2019 May 21;27(8):2442-2458.e5. doi: 10.1016/j.celrep.2019.04.079.


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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Chemokine CCL19 / metabolism
  • Chemokine CXCL13 / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / parasitology
  • Lymph Nodes / pathology
  • Lymphotoxin beta Receptor / metabolism
  • Lymphotoxin-alpha / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nematospiroides dubius / immunology
  • Nematospiroides dubius / pathogenicity
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction
  • Stromal Cells / cytology
  • Stromal Cells / metabolism


  • Chemokine CCL19
  • Chemokine CXCL13
  • Il4ra protein, mouse
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha
  • Receptors, Cell Surface