BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
By Brian P. O’Connor, V. Raman, L. Erickson, W. Cook, Lehn K. Weaver, Cory L. Ahonen, Ling-Li Lin, G. Mantchev, R. Bram, R. Noelle. Journal of Experimental Medicine, 2004
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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.
Subfields: Hematology, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/19ba3e780b16d952848797cef9d31b23c20772fe
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Citations in the corpus
- Osteoimmunology: interplay between the immune system and bone metabolism. (2006, background): “A BAFF/BLYS receptor, BCMA (B cell maturation factor), has recently been shown to be critical for long-term plasma cell survival (27, 28).”
- Competence and competition: the challenge of becoming a long-lived plasma cell (2006, background): “As well as TNF itself, survival factors could include B-cell-activating factor ( BAFF ) or a proliferation-inducing ligand ( APRIL ), both of which are ligands for the B-cell maturation antigen (BCMA) receptor, which is expressed by plasma cell”
- Regulation of plasma-cell development (2005, background): “IL-6, in conjunction with B-cell-activating factor (BAFF; also known as BLYS”
- From Vaccines to Memory and Back (2010, neutral): “It is believed that the bone marrow environment is particularly conducive for providing the necessary survival signals for plasma cells (Manz et al., 1997; O’Connor et al., 2004).”
- The regulation of IgA class switching (2008, background): “By contrast, engagement of BCMA by BAFF or APRIL delivers survival signals to plasma cell”
- Cracking the BAFF code (2009, background): “48 ), and BCMA expression is restricted to antibody-producing cell”
- Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. (2007, background): “Blockade of BAFF and APRIL decreases the number of bone marrow PCs in normal mice (O’Connor et al., 2004), raising the possibility that similar pharmacological inhibition might prove toxic to those MM cells that retain a microenvironmental dependence for NF-kB pathway activation.”