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BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma
Open accessAbstract
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.
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Citations
Cited by
The relation between inflammation and neurodegeneration in multiple sclerosis brains
Frischer, J. M., Bramow, S., Dal-Bianco, A., Lucchinetti, C. F., Rauschka, H., Schmidbauer, M., Laursen, H., Sorensen, P. S., & Lassmann, H. (2009) · Brain · doi:10.1093/brain/awp070 · Cited by 1,450
Astrocytes are active players in cerebral innate immunity
Farina, C., Aloisi, F., & Meinl, E. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.01.005 · Cited by 1,304
Self-citationAstrocyte barriers to neurotoxic inflammation
Sofroniew, M. V. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3898 · Cited by 1,202
Astrocyte Crosstalk in CNS Inflammation
Linnerbauer, M., Wheeler, M. A., & Quintana, F. J. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.012 · Cited by 989
B cell depletion therapies in autoimmune disease: advances and mechanistic insights
Lee, D. S. W., Rojas, O. L., & Gommerman, J. L. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00092-2 · Cited by 658
Metadata
- Authors
- Krumbholz, M., Theil, D., Derfuss, T., Rosenwald, A., Schrader, F., Monoranu, C.-M., Kalled, S. L., Hess, D. M., Serafini, B., Aloisi, F., Wekerle, H., Hohlfeld, R., & Meinl, E.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-01-10
- Volume
- 201
- Issue
- 2
- Pages
- 195-200
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2134203563
- Cited by
- 492
- References
- 0
- FWCI
- 21.69
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Krumbholz, M., Theil, D., Derfuss, T., Rosenwald, A., Schrader, F., Monoranu, C.-M., Kalled, S. L., Hess, D. M., Serafini, B., Aloisi, F., Wekerle, H., Hohlfeld, R., & Meinl, E. (2005). BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20041674
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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