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BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells

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 sur...

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Autores principales: O'Connor, Brian P., Raman, Vanitha S., Erickson, Loren D., Cook, W. James, Weaver, Lehn K., Ahonen, Cory, Lin, Ling-Li, Mantchev, George T., Bram, Richard J., Noelle, Randolph J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1887725/
https://www.ncbi.nlm.nih.gov/pubmed/14707116
http://dx.doi.org/10.1084/jem.20031330
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author O'Connor, Brian P.
Raman, Vanitha S.
Erickson, Loren D.
Cook, W. James
Weaver, Lehn K.
Ahonen, Cory
Lin, Ling-Li
Mantchev, George T.
Bram, Richard J.
Noelle, Randolph J.
author_facet O'Connor, Brian P.
Raman, Vanitha S.
Erickson, Loren D.
Cook, W. James
Weaver, Lehn K.
Ahonen, Cory
Lin, Ling-Li
Mantchev, George T.
Bram, Richard J.
Noelle, Randolph J.
author_sort O'Connor, Brian P.
collection PubMed
description 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.
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spelling pubmed-18877252008-03-11 BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells O'Connor, Brian P. Raman, Vanitha S. Erickson, Loren D. Cook, W. James Weaver, Lehn K. Ahonen, Cory Lin, Ling-Li Mantchev, George T. Bram, Richard J. Noelle, Randolph J. J Exp Med Article 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. The Rockefeller University Press 2004-01-05 /pmc/articles/PMC1887725/ /pubmed/14707116 http://dx.doi.org/10.1084/jem.20031330 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
O'Connor, Brian P.
Raman, Vanitha S.
Erickson, Loren D.
Cook, W. James
Weaver, Lehn K.
Ahonen, Cory
Lin, Ling-Li
Mantchev, George T.
Bram, Richard J.
Noelle, Randolph J.
BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
title BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
title_full BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
title_fullStr BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
title_full_unstemmed BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
title_short BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
title_sort bcma is essential for the survival of long-lived bone marrow plasma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1887725/
https://www.ncbi.nlm.nih.gov/pubmed/14707116
http://dx.doi.org/10.1084/jem.20031330
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