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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

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.
   
citation Dubey L K, Ludewig B, Luther S A, Harris N L. IL-4Rα-Expressing B Cells Are Required for CXCL13 Production by Fibroblastic Reticular Cells. Cell Rep 2019; 27:2442-2458.e5.
   
type journal paper/review (English)
date of publishing 21-5-2019
journal title Cell Rep (27/8)
ISSN electronic 2211-1247
pages 2442-2458.e5
PubMed 31116987
DOI 10.1016/j.celrep.2019.04.079