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

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.

SUBMITTER: Song J

PROVIDER: S-EPMC10206498 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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

Song Jian J Deshpande Tushar T Zhang Xueli X Hannocks Melanie-Jane MJ Lycke Nils N Cardell Susanna L SL Sorokin Lydia L

iScience 20230428 5

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 PDGFrecβhighCCL19lowgp38low fibroblastic reticular cells (FRC). In the absence of FRC expression of laminin α5 (pdgfrb- ...[more]

PMID: 37234087

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Project description:Thiele2013 - Lymph node germinal center cells The model of lymph node germinal center cells metabolism is derived from the community-driven global reconstruction of human metabolism (version 2.02, MODEL1109130000 ). This model is described in the article: A community-driven global reconstruction of human metabolism. Thiele I, et al . Nature Biotechnology Abstract: Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including ~2x more reactions and ~1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/. This model is hosted on BioModels Database and identified by: MODEL1310110036 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

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

Publications

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

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