BCR-Induced Ca2+ Signals Dynamically Tune Survival, Metabolic Reprogramming, and Proliferation of Naive B Cells.
Cell Rep
; 31(2): 107474, 2020 04 14.
Article
em En
| MEDLINE
| ID: mdl-32294437
ABSTRACT
B cell receptor (BCR) engagement induces naive B cells to differentiate and perform critical immune-regulatory functions. Acquisition of functional specificity requires that a cell survive, enter the cell cycle, and proliferate. We establish that quantitatively distinct Ca2+ signals triggered by variations in the extent of BCR engagement dynamically regulate these transitions by controlling nuclear factor κB (NF-κB), NFAT, and mTORC1 activity. Weak BCR engagement induces apoptosis by failing to activate NF-κB-driven anti-apoptotic gene expression. Stronger signals that trigger more robust Ca2+ signals promote NF-κB-dependent survival and NFAT-, mTORC1-, and c-Myc-dependent cell-cycle entry and proliferation. Finally, we establish that CD40 or TLR9 costimulation circumvents these Ca2+-regulated checkpoints of B cell activation and proliferation. As altered BCR signaling is linked to autoimmunity and B cell malignancies, these results have important implications for understanding the pathogenesis of aberrant B cell activation and differentiation and therapeutic approaches to target these responses.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos B
/
Cálcio
/
Células Precursoras de Linfócitos B
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos