NGFR regulates stromal cell activation in germinal centers
Summary: 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 spontaneou...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724000330 |
| _version_ | 1797291768610291712 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alberto Hernández-Barranco |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-07T19:42:29Z |
| format | Article |
| id | doaj.art-633cda8ce4e244e3af309d6246a7a4de |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T19:42:29Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-633cda8ce4e244e3af309d6246a7a4de2024-02-29T05:18:42ZengElsevierCell Reports2211-12472024-02-01432113705NGFR regulates stromal cell activation in germinal centersAlberto Hernández-Barranco0Vanesa Santos1Marina S. Mazariegos2Eduardo Caleiras3Laura Nogués4Frédéric Mourcin5Simon Léonard6Christelle Oblet7Steve Genebrier8Delphine Rossille9Alberto Benguría10Alba Sanz11Enrique Vázquez12Ana Dopazo13Alejo Efeyan14Ana Ortega-Molina15Michel Cogne16Karin Tarte17Héctor Peinado18Microenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), 28029 Madrid, SpainMicroenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), 28029 Madrid, SpainMicroenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain; Liver Injury and Inflammation Laboratory, Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University, 28040 Madrid, SpainHistopathology Unit, Biotechnology Program, Spanish National Cancer Research Center (CNIO), 28029 Madrid, SpainMicroenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), 28029 Madrid, SpainUMR U1236, University Rennes, INSERM, EFS Bretagne, Equipe Labellisée Ligue Contre le Cancer, 35000 Rennes, FranceUMR U1236, University Rennes, INSERM, EFS Bretagne, Equipe Labellisée Ligue Contre le Cancer, 35000 Rennes, FranceImmunology Department, Faculty of Medicine, Limoges University, CNRS Umr 7276, Inserm U1262, 87000 Limoges, FranceUMR U1236, University Rennes, INSERM, EFS Bretagne, Equipe Labellisée Ligue Contre le Cancer, 35000 Rennes, FranceUMR U1236, University Rennes, INSERM, EFS Bretagne, Equipe Labellisée Ligue Contre le Cancer, 35000 Rennes, France; SITI Lab, Pôle Biologie, CHU Rennes, 35000 Rennes, FranceGenomic Unit, Spanish National Cardiovascular Research, Carlos III, 28029 Madrid, SpainMetabolism and Cell Signaling Laboratory, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, SpainGenomic Unit, Spanish National Cardiovascular Research, Carlos III, 28029 Madrid, SpainGenomic Unit, Spanish National Cardiovascular Research, Carlos III, 28029 Madrid, SpainMetabolism and Cell Signaling Laboratory, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, SpainMetabolism and Cell Signaling Laboratory, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Metabolism in Cancer and Ageing Laboratory, Immune System and Function Department, Centro de Biología Molecular “Severo Ochoa” (CMBSO-CSIC), Madrid 28049, SpainUMR U1236, University Rennes, INSERM, EFS Bretagne, Equipe Labellisée Ligue Contre le Cancer, 35000 Rennes, FranceUMR U1236, University Rennes, INSERM, EFS Bretagne, Equipe Labellisée Ligue Contre le Cancer, 35000 Rennes, France; SITI Lab, Pôle Biologie, CHU Rennes, 35000 Rennes, FranceMicroenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724000330CP: Immunology |
| spellingShingle | 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 CP: Immunology |
| title | NGFR regulates stromal cell activation in germinal centers |
| title_full | NGFR regulates stromal cell activation in germinal centers |
| title_fullStr | NGFR regulates stromal cell activation in germinal centers |
| title_full_unstemmed | NGFR regulates stromal cell activation in germinal centers |
| title_short | NGFR regulates stromal cell activation in germinal centers |
| title_sort | ngfr regulates stromal cell activation in germinal centers |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724000330 |
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