Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow.
Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow.
复制标题
DOI：
10.1084/jem.20051611
复制
发表时间：
2005-12-05
期刊：
影响因子：
--
通讯作者：
Calame K
中科院分区：
文献类型：
--
作者：
Shapiro-Shelef M;Lin KI;Savitsky D;Liao J;Calame K
长寿的浆细胞主要存在于骨髓中，持续分泌抗体并提供体液记忆的重要组成部分。然而，当这些细胞分泌自身抗体或发生转化时，它们就可能致病。我们最近证明，转录抑制因子 B 淋巴细胞诱导成熟蛋白 1 (Blimp-1) 是浆细胞形成所必需的。为了确定Blimp-1在维持浆细胞中可能发挥的作用，我们培育了编码Blimp-1的基因可以以诱导方式被删除的小鼠。在体外或体内删除 Blimp-1 都会导致先前形成的 B220LOCD138HI 浆细胞丢失。通过掺入 BrdU，我们证实 Blimp-1 是维持骨髓中不分裂、长寿命浆细胞所必需的。 Blimp-1 也是长期维持血清中抗原特异性免疫球蛋白所必需的。因此，Blimp-1 不仅是长寿命浆细胞形成所必需的，也是其维持所必需的。这一发现为针对自身免疫和多发性骨髓瘤的新药物设计策略提供了可能性，重点是阻断 Blimp-1 表达或活性。
Long-lived plasma cells, residing primarily in the bone marrow, continuously secrete antibody and provide an important component of humoral memory. However, when such cells secrete autoantibodies or become transformed, they can be pathogenic. We have shown recently that the transcriptional repressor B lymphocyte–induced maturation protein 1 (Blimp-1) is required for the formation of plasma cells. To determine what role Blimp-1 might play in maintenance of plasma cells, we generated mice in which the gene encoding Blimp-1 could be deleted in an inducible manner. Deletion of Blimp-1 either in vitro or in vivo leads to loss of previously formed B220LOCD138HI plasma cells. Using BrdU incorporation, we confirmed that Blimp-1 is required for the maintenance of nondividing, long-lived plasma cells in the bone marrow. Blimp-1 is also required for long-term maintenance of antigen-specific immunoglobulin in serum. Thus Blimp-1 is required not only for the formation but also for the maintenance of long-lived plasma cells. This finding provides the possibility of new drug design strategies for autoimmunity and multiple myeloma focused on blocking Blimp-1 expression or activity.
登录
查看更多内容
DOI：
10.1084/jem.192.12.1841
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Reljic R;Wagner SD;Peakman LJ;Fearon DT
通讯作者：
Fearon DT
影响因子：
64.8
作者：
Reimold, AM;Iwakoshi, NN;Glimcher, LH
通讯作者：
Glimcher, LH
DOI：
10.1084/jem.20031330
发表时间：
2004-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
O'Connor BP;Raman VS;Erickson LD;Cook WJ;Weaver LK;Ahonen C;Lin LL;Mantchev GT;Bram RJ;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
56.9
作者：
Lin, Y;Wong, KK;Calame, K
通讯作者：
Calame, K
影响因子：
32.4
作者：
Shaffer, AL;Lin, KI;Staudt, LM
通讯作者：
Staudt, LM