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.

Additional Metadata
Persistent URL dx.doi.org/10.1038/s41467-020-17135-2, hdl.handle.net/1765/129157
Journal Nature Communications
Citation
Cosgrove, J. (Jason), Novkovic, M. (Mario), Albrecht, S. (Stefan), Pikor, N.B. (Natalia B.), Zhou, Z. (Zhaoukun), Onder, G, … Coles, M. (2020). B cell zone reticular cell microenvironments shape CXCL13 gradient formation. Nature Communications, 11(1). doi:10.1038/s41467-020-17135-2