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B cell zone reticular cell microenvironments shape CXCL13 gradient formation

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B cell zone reticular cell microenvironments shape CXCL13 gradient formation

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COSGROVE, Jason, Mario NOVKOVIC, Stefan ALBRECHT, Natalia B. PIKOR, Zhaoukun ZHOU, Daniel F. LEGLER, Mark C. LEAKE, Jon TIMMIS, Burkhard LUDEWIG, Mark C. COLES, 2020. B cell zone reticular cell microenvironments shape CXCL13 gradient formation. In: Nature Communications. Nature Publishing Group. 11(1), 3677. eISSN 2041-1723. Available under: doi: 10.1038/s41467-020-17135-2

@article{Cosgrove2020retic-51147, title={B cell zone reticular cell microenvironments shape CXCL13 gradient formation}, year={2020}, doi={10.1038/s41467-020-17135-2}, number={1}, volume={11}, journal={Nature Communications}, author={Cosgrove, Jason and Novkovic, Mario and Albrecht, Stefan and Pikor, Natalia B. and Zhou, Zhaoukun and Legler, Daniel F. and Leake, Mark C. and Timmis, Jon and Ludewig, Burkhard and Coles, Mark C.}, note={Article Number: 3677} }

Cosgrove, Jason 2020-10-01T07:41:58Z Legler, Daniel F. B cell zone reticular cell microenvironments shape CXCL13 gradient formation Ludewig, Burkhard 2020-10-01T07:41:58Z 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<sup>+</sup> 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. Novkovic, Mario Coles, Mark C. Timmis, Jon eng Zhou, Zhaoukun Albrecht, Stefan Albrecht, Stefan Legler, Daniel F. Ludewig, Burkhard Cosgrove, Jason 2020 Coles, Mark C. Leake, Mark C. Leake, Mark C. Attribution 4.0 International Timmis, Jon Zhou, Zhaoukun Pikor, Natalia B. Novkovic, Mario Pikor, Natalia B.

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