Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/17534
Title
NGFR regulates stromal cell activation in germinal centers.
Author(s)
Hernández-Barranco, Alberto | Santos, Vanesa | Mazariegos, Marina S | Caleiras, Eduardo | Nogués, Laura | Mourcin, Frédéric | Léonard, Simon | Oblet, Christelle | Genebrier, Steve | Rossille, Delphine | Benguría, Alberto | Sanz, Alba | Vázquez, Enrique | Dopazo, Ana CNIC | Efeyan, Alejo CNIO | Ortega-Molina, Ana CNIO | Cogne, Michel | Tarte, Karin | Peinado Selgas, Hector CNIO
Date issued
2024-01-30
Citation
Cell Rep . 2024 :113705.
Language
Inglés
Document type
journal article
Abstract
Nerve growth factor receptor (NGFR) is expressed by follicular dendritic cells (FDCs). However, the role of NGFR in the humoral response is not well defined. Here, we study the effect of Ngfr loss on lymph node organization and function, demonstrating that Ngfr depletion leads to spontaneous germinal center (GC) formation and an expansion of the GC B cell compartment. In accordance with this effect, stromal cells are altered in Ngfr-/- mice with a higher frequency of FDCs, characterized by CD21/35, MAdCAM-1, and VCAM-1 overexpression. GCs are located ectopically in Ngfr-/- mice, with lost polarization together with impaired high-affinity antibody production and an increase in circulating autoantibodies. We observe higher levels of autoantibodies in Bcl2 Tg/Ngfr-/- mice, concomitant with a higher incidence of autoimmunity and lower overall survival. Our work shows that NGFR is involved in maintaining GC structure and function, participating in GC activation, antibody production, and immune tolerance.
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