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NGFR regulates stromal cell activation in germinal centers.

Authors :
Hernández-Barranco A
Santos V
Mazariegos MS
Caleiras E
Nogués L
Mourcin F
Léonard S
Oblet C
Genebrier S
Rossille D
Benguría A
Sanz A
Vázquez E
Dopazo A
Efeyan A
Ortega-Molina A
Cogne M
Tarte K
Peinado H
Source :
Cell reports [Cell Rep] 2024 Feb 27; Vol. 43 (2), pp. 113705. Date of Electronic Publication: 2024 Feb 01.
Publication Year :
2024

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 <superscript>-/-</superscript> mice with a higher frequency of FDCs, characterized by CD21/35, MAdCAM-1, and VCAM-1 overexpression. GCs are located ectopically in Ngfr <superscript>-/-</superscript> 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 <superscript>-/-</superscript> 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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2211-1247
Volume :
43
Issue :
2
Database :
MEDLINE
Journal :
Cell reports
Publication Type :
Academic Journal
Accession number :
38307025
Full Text :
https://doi.org/10.1016/j.celrep.2024.113705