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Stromal cell-contact dependent PI3K and APRIL induced NF-κB signaling complement each other to prevent mitochondrial- and endoplasmic reticulum stress induced cell death of bone marrow plasma cells
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- SummaryPersistence of long-lived, memory plasma cells in the bone marrow depends on survival factors available in the bone marrow, provided in niches organized by stromal cells. Here we describe that ex vivo we can prevent apoptosis of bone marrow plasma cells by supplying direct cell contact with stromal cells and the soluble cytokine APRIL. Integrin-mediated contact of bone marrow plasma cells with stromal cells activates the PI3K signaling pathway, leading to critical inactivation of FoxO1/3 and preventing the activation of mitochondrial stress-associated effector caspases 3 and 7. Likely, inhibition of PI3K signaling in vivo ablates bone marrow plasma cells. APRIL signaling, via the 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 necessary and complementary signals to maintain bone marrow memory plasma cells.
- Subjects :
- 0303 health sciences
Programmed cell death
Stromal cell
biology
Chemistry
medicine.medical_treatment
Endoplasmic reticulum
3. Good health
Cell biology
03 medical and health sciences
0302 clinical medicine
Cytokine
medicine.anatomical_structure
Apoptosis
medicine
biology.protein
Bone marrow
PI3K/AKT/mTOR pathway
Caspase 12
030304 developmental biology
030215 immunology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....bf82a0753648337475bf83908b819a28