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Publication : The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation.

First Author  Song J Year  2023
Journal  iScience Volume  26
Issue  5 Pages  106753
PubMed ID  37234087 Mgi Jnum  J:338921
Mgi Id  MGI:7485367 Doi  10.1016/j.isci.2023.106753
Citation  Song J, et al. (2023) The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation. iScience 26(5):106753
abstractText  Germinal center (GC) formation and antibody production in lymph node follicles require coordinated interactions between B-cells, T-cells and dendritic cells (DCs), orchestrated by the extracellular matrix-rich reticular fiber (RF) network. We describe a unique laminin 523-containing RF network around and between follicles that associates with PDGFrecbeta(high)CCL19(low)gp38(low) fibroblastic reticular cells (FRC). In the absence of FRC expression of laminin alpha5 (pdgfrb-cre:Lama5(fl/fl)), pre-Tfh-cells, B-cells and DCs are displaced from follicle borders, correlating with fewer Tfh-cells and GC B-cells. Total DCs are not altered in pdgfrb-cre:Lama5(fl/fl) mice, but cDC2s, which localize to laminin alpha5 in RFs at follicle borders, are reduced. In addition, PDGFrecbeta(high)CCL19(low)gp38(low) FRCs show lower Ch25h expression, required for 7alpha,25-dihydroxycholesterol synthesis that attracts pre-Tfh-cells, B-cells and DCs to follicle borders. We propose that RF basement membrane components represent a type of tissue memory that guides the localization and differentiation of both specialized FRC and DC populations, required for normal lymph node function.
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