B-cell Zone Reticular Cell Microenvironments Shape CXCL13 Gradient Formation

Cosgrove, Jason, Novkovic, Mario, Pikor, Natalia, Zhou, Zhaokun, Onder, Lucas, Morbe, Urs, Cupovic, Jovana, Miller, Helen, Alden, Kieran, Thuery, Anne, O-Toole, Peter, Jarrett, Simon, Taylor, Emily, Venetz, Daniel, Heller, Manfred, Uguccioni, Mariagrazia, Legler, Daniel, Lacey, Charles, Coatesworth, Andrew, Polak, Wojciech, Cupedo, Tom, Manoury, Benedicte, Thelen, Marcus, Sten, Jen, Wolf, Marlene, Leake, Mark, Timmis, Jonathan, Ludewig, Berkhard and Coles, Mark (2020) B-cell Zone Reticular Cell Microenvironments Shape CXCL13 Gradient Formation. Nature Communications, 11. p. 3677. ISSN 2041-1723

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Abstract

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

Item Type: Article
Subjects: Computing > Artificial Intelligence
Sciences > Biomedical Sciences
Divisions: Faculty of Technology > School of Computer Science
Depositing User: Jonathan Timmis
Date Deposited: 26 May 2020 17:23
Last Modified: 27 Jul 2020 10:56
URI: http://sure.sunderland.ac.uk/id/eprint/12073
ORCID for Jonathan Timmis: ORCID iD orcid.org/0000-0003-1055-0471

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