BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma.
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.
Krumbholz
Markus
M
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, D-82152 Martinsried, Germany.
Theil
Diethilde
D
Derfuss
Tobias
T
Rosenwald
Andreas
A
Schrader
Frank
F
Monoranu
Camelia-Maria
CM
Kalled
Susan L
SL
Hess
Donna M
DM
Serafini
Barbara
B
Aloisi
Francesca
F
Wekerle
Hartmut
H
Hohlfeld
Reinhard
R
Meinl
Edgar
E
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
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