1. Follicular lymphoma triggers phenotypic and functional remodeling of the human lymphoid stromal cell landscape.
- Author
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Mourcin F, Verdière L, Roulois D, Amin R, Lamaison C, Sibut V, Thamphya B, Pangault C, Monvoisin C, Huet S, Seffals M, Baulande S, Mechta-Grigoriou F, Legoix P, Rossille D, Guirriec M, Léonard S, Cartron G, Salles G, Fest T, and Tarte K
- Subjects
- Cells, Cultured, Chemokine CCL19 metabolism, Chemokine CCL21 metabolism, Humans, Integrin alpha1 metabolism, Palatine Tonsil cytology, Signal Transduction immunology, Stromal Cells cytology, Transforming Growth Factor beta1 genetics, Transforming Growth Factor beta1 metabolism, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, B-Lymphocytes immunology, Dendritic Cells immunology, Lymphoma, Follicular immunology, Lymphoma, Follicular pathology, Palatine Tonsil immunology, Stromal Cells immunology
- Abstract
Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing, and functional assays, defining three distinct human LSC subsets. The integrin CD49a designated perivascular stromal cells exhibiting features of local committed LSC precursors and segregated cytokine and chemokine-producing fibroblastic reticular cells (FRCs) supporting B and T cell survival. The follicular dendritic cell transcriptional profile reflected active responses to B cell and non-B cell stimuli. We therefore examined the effect of B cell stimuli on LSCs in follicular lymphoma (FL). FL B cells interacted primarily with CD49a
+ FRCs. Transcriptional analyses revealed LSC reprogramming in situ downstream of the cytokines tumor necrosis factor (TNF) and transforming growth factor β (TGF-β), including increased expression of the chemokines CCL19 and CCL21. Our findings define human LSC populations in healthy tissue and reveal bidirectional crosstalk between LSCs and malignant B cells that may present a targetable axis in lymphoma., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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