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

B细胞激活因子 骨髓 免疫学 生物 抗原 等离子体电池 互动者 抗体 细胞生物学 B细胞 癌症研究
作者
Brian P. O’Connor,Vanitha S. Raman,Loren D. Erickson,W. James Cook,Lehn K. Weaver,Cory L. Ahonen,Ling-Li Lin,George T. Mantchev,Richard J. Bram,Randolph J. Noelle
出处
期刊:Journal of Experimental Medicine [Rockefeller University Press]
卷期号:199 (1): 91-98 被引量:1025
标识
DOI:10.1084/jem.20031330
摘要

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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