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

2005; Rockefeller University Press; Volume: 201; Issue: 2 Linguagem: Inglês

10.1084/jem.20041674

1540-9538

Markus Krumbholz, Diethilde Theil, Tobias Derfuß, Andreas Rosenwald, Frank Schrader, Camelia‐Maria Monoranu, Susan L. Kalled, Donna M. Hess, Barbara Serafini, Francesca Aloisi, Hartmut Wekerle, Reinhard Hohlfeld, Edgar Meinl,

Immunotherapy and Immune Responses

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.