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

Jian Song; Tushar Deshpande; Xueli Zhang; Melanie-Jane Hannocks; Nils Lycke; Susanna L Cardell; Lydia Sorokin

doi:10.1016/j.isci.2023.106753

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

iScience. 2023 Apr 28;26(5):106753. doi: 10.1016/j.isci.2023.106753. eCollection 2023 May 19.

Authors

Jian Song¹, Tushar Deshpande¹, Xueli Zhang¹, Melanie-Jane Hannocks¹, Nils Lycke², Susanna L Cardell², Lydia Sorokin¹

Affiliations

¹ Institute of Physiological Chemistry and Pathobiochemistry and Cells-in-Motion Interfaculty Centre (CIMIC), University of Muenster, 48149 Muenster, Germany.
² Department of Microbiology and Immunology, University of Gothenburg, 40530 Gothenburg, Sweden.

Abstract

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 PDGFrecβ^highCCL19^lowgp38^low fibroblastic reticular cells (FRC). In the absence of FRC expression of laminin α5 (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 α5 in RFs at follicle borders, are reduced. In addition, PDGFrecβ^highCCL19^lowgp38^low FRCs show lower Ch25h expression, required for 7α,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.

Keywords: Biological sciences; Immune response; Immune system; Immunology.