B cell zone reticular cell microenvironments shape CXCL13 gradient formation
Journal Paper/Review - Jul 22, 2020
Cosgrove Jason, Uguccioni Mariagrazia, Legler Daniel F, Lacey Charles J, Coatesworth Andrew, Polak Wojciech G, Cupedo Tom, Manoury Bénedicte, Thelen Marcus, Stein Jens V, Wolf Marlene, Leake Mark C, Timmis Jon, Ludewig Burkhard, Heller Manfred, Venetz Daniel, Taylor Emily, Novkovic Mario, Albrecht Stefan, Pikor Natalia, Zhou Zhaoukun, Onder Lucas, Mörbe Urs, Cupovic Jovana, Miller Helen, Alden Kieran, Thuery Anne, O'Toole Peter, Pinter Rita, Jarrett Simon, Coles Mark C
Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13 follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients.