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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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Publisher copy:
10.1038/s41467-020-17135-2

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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:
2041-1723


Language:
English
Keywords:
Pubs id:
1112141
Local pid:
pubs:1112141
Deposit date:
2020-06-15

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