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

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-4R alpha-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.