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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. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Alberto Hernández-Barranco, Vanesa Santos, Marina S Mazariegos, Eduardo Caleiras, Laura Nogués, Frédéric Mourcin, Simon Léonard, Christelle Oblet, Steve Genebrier, Delphine Rossille, Alberto Benguría, Alba Sanz, Enrique Vázquez, Ana Dopazo, Alejo Efeyan, Ana Ortega-Molina, Michel Cogne, Karin Tarte, Héctor Peinado. NGFR regulates stromal cell activation in germinal centers. Cell reports. 2024 Feb 27;43(2):113705

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PMID: 38307025

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