B cell zone reticular cell microenvironments shape CXCL13 gradient formation

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...

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Bibliographic Details
Published in:Nature communications Vol. 11; no. 1; pp. 3677 - 15
Main Authors: Cosgrove, Jason, Novkovic, Mario, Albrecht, Stefan, Pikor, Natalia B., Zhou, Zhaoukun, Onder, Lucas, Mörbe, Urs, Cupovic, Jovana, Miller, Helen, Alden, Kieran, Thuery, Anne, O’Toole, Peter, Pinter, Rita, Jarrett, Simon, Taylor, Emily, Venetz, Daniel, Heller, Manfred, Uguccioni, Mariagrazia, Legler, Daniel F., Lacey, Charles J., Coatesworth, Andrew, Polak, Wojciech G., Cupedo, Tom, Manoury, Bénedicte, Thelen, Marcus, Stein, Jens V., Wolf, Marlene, Leake, Mark C., Timmis, Jon, Ludewig, Burkhard, Coles, Mark C.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 22.07.2020
Nature Publishing Group
Nature Portfolio
Subjects:
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Adaptive Immunity
Animals
B-Lymphocytes - cytology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Cancer
Cathepsin B
Cathepsin B - genetics
Cathepsin B - metabolism
Cell Behavior
Cell Line
Cellular Biology
Cellular Microenvironment - immunology
Chemokine CXCL13 - immunology
Chemokine CXCL13 - metabolism
Chemokines
Computer Simulation
Concentration gradient
CXCL13 protein
Dendritic Cells, Follicular - cytology
Dendritic Cells, Follicular - immunology
Dendritic Cells, Follicular - metabolism
Extracellular matrix
Extracellular Matrix - metabolism
Homing behavior
Humanities and Social Sciences
Humans
Immunology
Innate immunity
Life Sciences
Lymph nodes
Lymphatic system
Mathematical models
Mice
Mice, Knockout
Microenvironments
Microscopy, Fluorescence
Models, Biological
multidisciplinary
Nodes
Optimization
Palatine Tonsil - cytology
Phenotypes
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Recombinant Proteins - metabolism
Science
Science (multidisciplinary)
Solubilization
Stromal Cells - immunology
Stromal Cells - metabolism
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Morphogens such as chemokines form gradients to direct graded responses and modulate cell behaviors. Here the authors show, using imaging and computer simulation, that the chemokine CXCL13 originated from follicular reticular cells in the lymph nodes forms both soluble and immobilized gradients to regulate B cell recruitment and migration.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-17135-2