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.
Cosgrove J, Novkovic M, Albrecht S, Pikor N, Zhou Z, Onder L, Mörbe
U, Cupovic J, Miller H, Alden K, Thuery A, O'Toole P, Pinter R,
Jarrett S, Taylor E, Venetz D, Heller M, Uguccioni M, Legler D F,
Lacey C J, Coatesworth A, Polak W G, Cupedo T, Manoury B, Thelen M,
Stein J V, Wolf M, Leake M C, Timmis J, Ludewig B, Coles M C. B cell
zone reticular cell microenvironments shape CXCL13 gradient
formation. Nat Commun 2020; 11:3677.