Journal article
B cell zone reticular cell microenvironments shape CXCL13 gradient formation
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 9.2MB, Terms of use)
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(Supplementary materials, Version of record, 8.6MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-020-17135-2
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Communications More from this journal
- Volume:
- 11
- Article number:
- 3677
- Publication date:
- 2020-07-22
- Acceptance date:
- 2020-03-12
- DOI:
- EISSN:
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2041-1723
- Language:
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English
- Keywords:
- Pubs id:
-
1112141
- Local pid:
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pubs:1112141
- Deposit date:
-
2020-06-15
Terms of use
- Copyright holder:
- Cosgrove et al.
- Copyright date:
- 2020
- Rights statement:
- © The Authors 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
- Licence:
- CC Attribution (CC BY)
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