BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma |
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Authors: | Krumbholz Markus Theil Diethilde Derfuss Tobias Rosenwald Andreas Schrader Frank Monoranu Camelia-Maria Kalled Susan L Hess Donna M Serafini Barbara Aloisi Francesca Wekerle Hartmut Hohlfeld Reinhard Meinl Edgar |
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Affiliation: | Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, D-82152 Martinsried, Germany. |
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Abstract: | We report that B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) is expressed in the normal human brain at approximately 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-gamma and TNF-alpha 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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