BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma.

BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma.
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BAFF由星形胶质细胞产生,并在多发性硬化病变和原发性中枢神经系统淋巴瘤中上调。

DOI:
10.1084/jem.20041674
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发表时间:
2005-01-17
影响因子:
15.3
通讯作者:
Meinl, E
Meinl, E
中科院分区:
医学1区
文献类型:
--
作者:
Krumbholz, M;Theil, D;Derfuss, T;Rosenwald, A;Schrader, F;Monoranu, CM;Kalled, SL;Hess, DM;Serafini, B;Aloisi, F;Wekerle, H;Hohlfeld, R;Meinl, E

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我们报道了肿瘤坏死因子(TNF)家族的B细胞活化因子(BAFF)在正常人脑中的表达量为淋巴组织(扁桃体和腺样体)的10%,并由星形胶质细胞产生。用酶联免疫吸附法定期检测脑组织裂解液和正常脊髓液中的BAFF,用双荧光显微镜检测星形胶质细胞中的BAFF。培养的人星形胶质细胞在干扰素-γ和TNF-α刺激后,通过类似于糠蛋白的蛋白酶依赖途径分泌功能活跃的BAFF。活化星形胶质细胞的每细胞BAFF分泌量远高于单核细胞和巨噬细胞。我们研究了含有B细胞成分的脑病变,发现在多发性硬化症斑块中,BAFF的表达被强烈上调至淋巴组织中观察到的水平。BAFF定位于靠近表达BAFF- r的免疫细胞的星形胶质细胞。BAFF受体在原发性中枢神经系统(CNS)淋巴瘤中原位强表达。本文确定星形胶质细胞是BAFF的非免疫来源。中枢神经系统产生的BAFF可能支持炎性疾病和原发性B细胞淋巴瘤中的B细胞存活。
We report that B cell–activating factor of the tumor necrosis factor (TNF) family (BAFF) is expressed in the normal human brain at ∼10% of that in lymphatic tissues (tonsils and adenoids) and is produced by astrocytes. BAFF was regularly detected by enzyme-linked immunosorbent assay in brain tissue lysates and in normal spinal fluid, and in astrocytes by double fluorescence microscopy. Cultured human astrocytes secreted functionally active BAFF after stimulation with interferon-γ and TNF-α via a furin-like protease-dependent pathway. BAFF secretion per cell was manifold higher in activated astrocytes than in monocytes and macrophages. We studied brain lesions with B cell components, and found that in multiple sclerosis plaques, BAFF expression was strongly up-regulated to levels observed in lymphatic tissues. BAFF was localized in astrocytes close to BAFF-R–expressing immune cells. BAFF receptors were strongly expressed in situ in primary central nervous system (CNS) lymphomas. This paper identifies astrocytes as a nonimmune source of BAFF. CNS-produced BAFF may support B cell survival in inflammatory diseases and primary B cell lymphoma.
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