BCMA is essential for the survival of long-lived bone marrow plasma cells.
BCMA is essential for the survival of long-lived bone marrow plasma cells.
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DOI：
10.1084/jem.20031330
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发表时间：
2004-01-05
期刊：
影响因子：
--
通讯作者：
Noelle RJ
中科院分区：
文献类型：
--
作者：
O'Connor BP;Raman VS;Erickson LD;Cook WJ;Weaver LK;Ahonen C;Lin LL;Mantchev GT;Bram RJ;Noelle RJ
长寿命的体液免疫表现为骨髓浆细胞（PC）能够长时间存活。最近的研究已经强调了BLyS和APRIL作为可以支持B谱系淋巴细胞存活的因子的重要性。我们表明BLyS可以在体外维持PC存活，并且白细胞介素6可以进一步增强这种存活。BLyS选择性上调PC中的Mcl-1，表明这种α-凋亡基因产物可能在PC存活中起重要作用。通过跨膜激活剂和亲环素配体相互作用物-免疫球蛋白治疗，阻断BLyS抑制体外和体内PC存活。相对于静息B细胞，PC中B细胞成熟抗原（BCMA）的表达升高，跨膜激活因子和亲环素配体相互作用因子和BAFF受体的表达降低，表明BCMA在PC存活中起重要作用。BCMA−/−小鼠的研究证实了BCMA在PC存活中的重要性，与野生型对照相比，BCMA−/−小鼠中长寿命骨髓PC的存活受损。这些发现为PC长期存活的分子基础提供了新的见解。
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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DOI：
10.1038/nsb769
发表时间：
2002-04-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Oren, DA;Li, YL;Arnold, E
通讯作者：
Arnold, E
DOI：
10.1084/jem.20011626
发表时间：
2002-03-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
O'Connor BP;Cascalho M;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
9.2
作者：
Marsters, SA;Yan, MH;Ashkenazi, A
通讯作者：
Ashkenazi, A
影响因子：
56.9
作者：
Bouillet, P;Metcalf, D;Strasser, A
通讯作者：
Strasser, A
影响因子：
5.6
作者：
Karpusas, M;Cachero, TG;Kalled, SL
通讯作者：
Kalled, SL