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BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2004
- Publisher :
- The Rockefeller University Press, 2004.
-
Abstract
- Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by interleukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this α-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in vitro and in vivo. Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival. Affirmation of the importance of BCMA in PC survival was provided by studies in BCMA−/− mice in which the survival of long-lived bone marrow PCs was impaired compared with wild-type controls. These findings offer new insights into the molecular basis for the long-term survival of PCs.
- Subjects :
- Cell Survival
Cellular differentiation
Immunology
Plasma Cells
Bone Marrow Cells
Biology
Article
Receptors, Tumor Necrosis Factor
03 medical and health sciences
Mice
0302 clinical medicine
Immunophenotyping
immunophenotyping
B-Cell Activating Factor
medicine
B lymphocyte subsets
Immunology and Allergy
Animals
B-Cell Maturation Antigen
BAFF receptor
B-cell activating factor
cell lineage
030304 developmental biology
DNA Primers
Peptidylprolyl isomerase
Mice, Knockout
0303 health sciences
Mice, Inbred BALB C
Base Sequence
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Transmembrane activator and CAML interactor
Membrane Proteins
antibody formation
Mice, Inbred C57BL
cell differentiation
medicine.anatomical_structure
Cancer research
Bone marrow
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 15409538 and 00221007
- Volume :
- 199
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....786c6ac68268ddf14d1365bad2251ff8