B cell zone reticular cell microenvironments shape CXCL13 gradient formation

Nat Commun. 2020 Jul 22;11(1):3677. doi: 10.1038/s41467-020-17135-2.

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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cathepsin B / genetics
  • Cathepsin B / metabolism
  • Cell Line
  • Cellular Microenvironment / immunology*
  • Chemokine CXCL13 / immunology
  • Chemokine CXCL13 / metabolism*
  • Computer Simulation
  • Dendritic Cells, Follicular / cytology
  • Dendritic Cells, Follicular / immunology*
  • Dendritic Cells, Follicular / metabolism
  • Extracellular Matrix / metabolism
  • Humans
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Models, Biological
  • Palatine Tonsil / cytology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Stromal Cells / immunology
  • Stromal Cells / metabolism

Substances

  • CXCL13 protein, human
  • Chemokine CXCL13
  • Cxcl13 protein, mouse
  • Recombinant Proteins
  • CTSB protein, human
  • Cathepsin B
  • Ctsb protein, mouse