SLAM family receptors control pro-survival effectors in germinal center B cells to promote humoral immunity.
Animals
Antibodies
/ metabolism
Antibody Formation
/ immunology
Antigens, Helminth
/ metabolism
Apoptosis
B-Lymphocytes
/ cytology
Bone Marrow
/ metabolism
Cell Count
Cell Cycle
Cell Proliferation
Cell Survival
Dose-Response Relationship, Immunologic
Germinal Center
/ cytology
Immunity, Humoral
Immunization
Immunoglobulin Class Switching
Immunologic Memory
Mice, Knockout
Nematospiroides dubius
/ physiology
Plasma Cells
/ metabolism
Proto-Oncogene Proteins c-bcl-2
/ metabolism
Signal Transduction
Signaling Lymphocytic Activation Molecule Family
/ deficiency
Somatic Hypermutation, Immunoglobulin
T-Lymphocytes
/ cytology
T-Lymphocytes, Helper-Inducer
/ metabolism
Vaccination
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
19
04
2020
revised:
31
08
2020
accepted:
20
10
2020
entrez:
25
11
2020
pubmed:
26
11
2020
medline:
15
9
2021
Statut:
ppublish
Résumé
Expression of the signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is critical for the germinal center (GC) reaction and T cell-dependent antibody production. However, when SAP is expressed normally, the role of the associated SLAM family receptors (SFRs) in these processes is nebulous. Herein, we established that in the presence of SAP, SFRs suppressed the expansion of the GC reaction but facilitated the generation of antigen-specific B cells and antibodies. SFRs favored the generation of antigen-reactive B cells and antibodies by boosting expression of pro-survival effectors, such as the B cell antigen receptor (BCR) and Bcl-2, in activated GC B cells. The effects of SFRs on the GC reaction and T cell-dependent antibody production necessitated expression of multiple SFRs, both in T cells and in B cells. Hence, while in the presence of SAP, SFRs inhibit the GC reaction, they are critical for the induction of T cell-mediated humoral immunity by enhancing expression of pro-survival effectors in GC B cells.
Identifiants
pubmed: 33237304
pii: 211564
doi: 10.1084/jem.20200756
pmc: PMC7694575
pii:
doi:
Substances chimiques
Antibodies
0
Antigens, Helminth
0
Proto-Oncogene Proteins c-bcl-2
0
Signaling Lymphocytic Activation Molecule Family
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CIHR
ID : MT-14429
Pays : Canada
Organisme : CIHR
ID : MOP-82906
Pays : Canada
Organisme : CIHR
ID : FDN-143338
Pays : Canada
Organisme : CIHR
ID : PJT-166028
Pays : Canada
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Zhong et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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