Stromal Cell-Contact Dependent PI3K and APRIL Induced NF-κB Signaling Prevent Mitochondrial- and ER Stress Induced Death of Memory Plasma Cells.
Cell Rep
; 32(5): 107982, 2020 08 04.
Article
en En
| MEDLINE
| ID: mdl-32755576
ABSTRACT
The persistence of long-lived memory plasma cells in the bone marrow depends on survival factors available in the bone marrow, which are provided in niches organized by stromal cells. Using an ex vivo system in which we supply the known survival signals, direct cell contact to stromal cells, and the soluble cytokine a proliferation-inducing ligand (APRIL), we have elucidated the critical signaling pathways required for the survival of long-lived plasma cells. Integrin-mediated contact of bone marrow plasma cells with stromal cells activates the phosphatidylinositol 3-kinase (PI3K) signaling pathway, leading to critical inactivation of Forkhead-Box-Protein O1/3 (FoxO1/3) and preventing the activation of mitochondrial stress-associated effector caspases 3 and 7. Accordingly, inhibition of PI3K signaling in vivo ablates bone marrow plasma cells. APRIL signaling, by the nuclear factor κB (NF-κB) pathway, blocks activation of the endoplasmic-reticulum-stress-associated initiator caspase 12. Thus, stromal-cell-contact-induced PI3K and APRIL-induced NF-κB signaling provide the necessary and complementary signals to maintain bone marrow memory plasma cells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Plasmáticas
/
FN-kappa B
/
Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral
/
Fosfatidilinositol 3-Quinasa
/
Estrés del Retículo Endoplásmico
/
Memoria Inmunológica
/
Mitocondrias
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania