The Journal of Experimental Medicine
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Published online 10 January 2005 doi:10.1084/jem.20041674
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 2, 195-200
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*Lymphoma
*Multiple Sclerosis
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BRIEF DEFINITIVE REPORT

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

Markus Krumbholz1, Diethilde Theil2, Tobias Derfuss1,3, Andreas Rosenwald4, Frank Schrader1, Camelia-Maria Monoranu4, Susan L. Kalled5, Donna M. Hess5, Barbara Serafini6, Francesca Aloisi6, Hartmut Wekerle1, Reinhard Hohlfeld1,3, and Edgar Meinl1,3

1 Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, D-82152 Martinsried, Germany
2 Department of Neurology, Ludwig-Maximilians-University, D-81377 Munich, Germany
3 Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University, D-81377 Munich, Germany
4 Institute of Pathology, University of Würzburg, D-97080 Würzburg, Germany
5 Biogen Idec Inc., Cambridge, MA 02142
6 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, I-00161 Rome, Italy

CORRESPONDENCE Edgar Meinl: meinl{at}neuro.mpg.de

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-{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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