Analysis of Glucocorticoid Receptors and Their Apoptotic Response to Dexamethasone in Male Murine B Cells During Development
Analysis of Glucocorticoid Receptors and Their Apoptotic Response to Dexamethasone in Male Murine B Cells During Development
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DOI：
10.1210/en.2013-1473
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发表时间：
2014-02-01
期刊：
影响因子：
4.8
通讯作者：
Cidlowski, John A.
中科院分区：
文献类型：
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作者：
Gruver-Yates, Amanda L.;Quinn, Matthew A.;Cidlowski, John A.
糖皮质激素在炎症的消退中具有重要作用，并且在临床上它们通常用于治疗过敏、哮喘、败血症和自身免疫性疾病。此外，糖皮质激素被公认为通过诱导细胞凋亡对免疫系统中T细胞的发育和功能产生负面影响。然而，对糖皮质激素在B淋巴细胞中的作用知之甚少。在此，我们证明了糖皮质激素受体（GR）存在于从脾脏和骨髓分离的B细胞群中。发现B细胞群体比来自脾和骨髓的非B细胞群体表达更多的GR。GR蛋白存在于从脾脏分离的所有B细胞（B220+）发育亚群（成熟IgM+IgD+、不成熟IgM+IgD-和Pro/Pre IgM-IgD-）中。GR染色强度在B细胞发育亚群中不同，并且发现从脾（次级淋巴器官）分离的B细胞中的GR染色强度高于骨髓（初级淋巴器官）。小鼠脾细胞和骨髓淋巴细胞的体外细胞培养表明，地塞米松刺激所有B细胞发育亚群的细胞凋亡，表明糖皮质激素的反应。此外，在体内给予地塞米松肾上腺切除小鼠减少B细胞数量在脾脏和骨髓。这些数据表明，糖皮质激素信号在B细胞的生死决定中具有重要的未充分研究的作用。
Glucocorticoids have an important role in the resolution of inflammation and clinically they are routinely used to treat allergies, asthma, sepsis, and autoimmune diseases. In addition, glucocorticoids are well recognized to negatively impact the development and function of T cells in the immune system by inducing apoptosis. Less is known however about glucocorticoid function in B lymphocytes. Herein, we demonstrate that the glucocorticoid receptor (GR) is present in B-cell populations isolated from both the spleen and the bone marrow. B-cell populations were found to express more GR than non-B-cell populations from both the spleen and the bone marrow. GR protein was found in all B-cell (B220+) developmental subsets (Mature IgM+IgD+, Immature IgM+IgD-, and Pro/Pre IgM-IgD-) isolated from spleen. GR staining intensity was varied among the B-cell developmental subsets and was found to be higher in B cells isolated from the spleen (secondary lymphoid organ) versus the bone marrow (primary lymphoid organ). Ex vivo cell culture of murine splenocytes and bone marrow lymphocytes indicated that dexamethasone stimulated apoptosis in all B-cell developmental subsets demonstrating glucocorticoid responsiveness. Furthermore, in vivo administration of dexamethasone to adrenalectomized mice reduced B-cell numbers in both spleen and bone marrow. These data suggest that glucocorticoid signaling has an important understudied role in B-cell life-or-death decisions.