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

Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling Li Lin, George T. Mantchev, Richard J. Bram, Randolph J. Noelle

Research output: Contribution to journalArticlepeer-review

644 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalJournal of Experimental Medicine
Volume199
Issue number1
DOIs
StatePublished - Jan 5 2004

Keywords

  • Antibody formation
  • B lymphocyte subsets
  • Cell differentiation
  • Cell lineage
  • Immunophenotyping

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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