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

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.

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