title: BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma.
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.
authors.affiliation: Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, D-82152 Martinsried, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krumbholz
authors.forename: Diethilde
authors.initials: D
authors.lastname: Theil
authors.forename: Tobias
authors.initials: T
authors.lastname: Derfuss
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Frank
authors.initials: F
authors.lastname: Schrader
authors.forename: Camelia-Maria
authors.initials: CM
authors.lastname: Monoranu
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kalled
authors.forename: Donna M
authors.initials: DM
authors.lastname: Hess
authors.forename: Barbara
authors.initials: B
authors.lastname: Serafini
authors.forename: Francesca
authors.initials: F
authors.lastname: Aloisi
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
mesh_terms: D001253:Astrocytes / Q000378:metabolism*; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes; D001921:Brain / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000378:metabolism*; D006801:Humans; D008223:Lymphoma / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000378:metabolism*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D008565:Membrane Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha