NR4A nuclear receptors restrain B cell responses to antigen when second signals are absent or limiting.

Animals B-Lymphocytes / immunology Cell Communication Cell Proliferation Cells, Cultured DNA-Binding Proteins / genetics Immunity, Humoral Immunomodulation Lymphocyte Activation Mice Mice, Knockout Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics Receptors, Antigen, B-Cell / metabolism Receptors, Steroid / genetics Receptors, Thyroid Hormone / genetics Signal Transduction T-Lymphocytes, Helper-Inducer / immunology

Journal

Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354

Informations de publication

Date de publication:
10 2020
Historique:
received: 30 03 2020
accepted: 17 07 2020
pubmed: 2 9 2020
medline: 7 1 2021
entrez: 2 9 2020
Statut: ppublish

Résumé

Antigen stimulation (signal 1) triggers B cell proliferation and primes B cells to recruit, engage and respond to T cell help (signal 2). Failure to receive signal 2 within a defined time window results in B cell apoptosis, yet the mechanisms that enforce dependence on co-stimulation are incompletely understood. Nr4a1-3 encode a small family of orphan nuclear receptors that are rapidly induced by B cell antigen receptor stimulation. Here, we show that Nr4a1 and Nr4a3 play partially redundant roles to restrain B cell responses to antigen in the absence of co-stimulation and do so, in part, by repressing the expression of BATF and, consequently, MYC. The NR4A family also restrains B cell access to T cell help by repressing expression of the T cell chemokines CCL3 and CCL4, as well as CD86 and ICAM1. Such NR4A-mediated regulation plays a role specifically under conditions of competition for limiting T cell help.

Identifiants

DOI: 10.1038/s41590-020-0765-7 PMID: 32868928 PMC: PMC8081071
pubmed: 32868928
doi: 10.1038/s41590-020-0765-7
pii: 10.1038/s41590-020-0765-7
pmc: PMC8081071
mid: NIHMS1613365
doi:

Substances chimiques

DNA-Binding Proteins 0
NR4A3 protein, human 0
Nr4a1 protein, mouse 0
Nuclear Receptor Subfamily 4, Group A, Member 1 0
Receptors, Antigen, B-Cell 0
Receptors, Steroid 0
Receptors, Thyroid Hormone 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1267-1279

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI148487
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR069520
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007334
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Commentaires et corrections

Type : CommentIn

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Auteurs

Corey Tan (C)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.
Biomedical Sciences (BMS) Graduate Program, University of California, San Francisco, CA, USA.

Ryosuke Hiwa (R)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.
ORCID: 0000-0001-6968-5712

James L Mueller (JL)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.

Vivasvan Vykunta (V)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.
ORCID: 0000-0002-5409-8635

Kenta Hibiya (K)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.

Mark Noviski (M)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.
Biomedical Sciences (BMS) Graduate Program, University of California, San Francisco, CA, USA.
ORCID: 0000-0001-8072-1059

John Huizar (J)

HHMI Medical Fellows Program, School of Medicine, University of California, San Francisco, CA, USA.

Jeremy F Brooks (JF)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.

Jose Garcia (J)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.

Cheryl Heyn (C)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA.
ORCID: 0000-0002-2531-9005

Zhongmei Li (Z)

J. David Gladstone Institutes, San Francisco, CA, USA.
Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA, USA.
Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
Innovative Genomics Institute, University of California, Berkeley, CA, USA.
Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
Chan Zuckerberg Biohub, San Francisco, CA, USA.

Alexander Marson (A)

J. David Gladstone Institutes, San Francisco, CA, USA.
Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA, USA.
Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
Innovative Genomics Institute, University of California, Berkeley, CA, USA.
Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
Chan Zuckerberg Biohub, San Francisco, CA, USA.
ORCID: 0000-0002-2734-5776

Julie Zikherman (J)

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, USA. julie.zikherman@ucsf.edu.
ORCID: 0000-0002-0873-192X

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes B › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Communication cellulaire › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Cellules › Cellules cultivées › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité humorale › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunomodulation › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des lymphocytes › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Membre-1 du groupe A de la sous-famille-4 de récepteurs nucléaires › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs pour l'antigène des lymphocytes B › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs aux stéroïdes › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs des hormones thyroïdiennes › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › NR4A nuclear receptors restrain B cell...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T auxiliaires › NR4A nuclear receptors restrain B cell...