B cell zone reticular cell microenvironments shape CXCL13 gradient formation.

Nature Communications
Jason CosgroveMark C Coles

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.

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Citations

Jan 6, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natalia Barbara PikorBurkhard Ludewig
May 12, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Mathieu RouanneAurélien Marabelle
Jul 4, 2021·Seminars in Immunology·Shabnam Shalapour, Michael Karin
Jul 15, 2021·Trends in Immunology·Lushen LiJonathan S Bromberg
May 29, 2021·Cardiovascular Research·Margarete HeinrichsGustavo Campos Ramos
Jul 30, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer L Gommerman, Jeffrey L Browning
Nov 12, 2021·Cell and Tissue Research·Wafaa MahmoudWolfgang Kummer

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Methods Mentioned

BETA
flow cytometry
confocal microscopy
fluorescence microscopy
FACS
PCR

Software Mentioned

MOEA
R
Imaris
SPARTAN
ncf
ADEMS
custom
NSGA
II
iGraph

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