The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
BAFF and MyD88 signals promote a lupuslike disease independent of T cells
Open accessAbstract
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. However, the underlying cause of disease appears to relate to defects in T cell tolerance or T cell help to B cells. Transgenic (Tg) mice overexpressing the cytokine B cell–activating factor of the tumor necrosis factor family (BAFF) develop an autoimmune disorder similar to SLE and show impaired B cell tolerance and altered T cell differentiation. We generated BAFF Tg mice that were completely deficient in T cells, and, surprisingly, these mice developed an SLE-like disease indistinguishable from that of BAFF Tg mice. Autoimmunity in BAFF Tg mice did, however, require B cell–intrinsic signals through the Toll-like receptor (TLR)–associated signaling adaptor MyD88, which controlled the production of proinflammatory autoantibody isotypes. TLR7/9 activation strongly up-regulated expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), which is a receptor for BAFF involved in B cell responses to T cell–independent antigens. Moreover, BAFF enhanced TLR7/9 expression on B cells and TLR-mediated production of autoantibodies. Therefore, autoimmunity in BAFF Tg mice results from altered B cell tolerance, but requires TLR signaling and is independent of T cell help. It is possible that SLE patients with elevated levels of BAFF show a similar basis for disease.
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Cites
1 retracted
RETRACTED ARTICLE: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL
Litinskiy, M. B., Nardelli, B., Hilbert, D. M., He, B., Schaffer, A., Casali, P., & Cerutti, A. (2002) · Nature Immunology · doi:10.1038/ni829 · Cited by 1,252
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Targeted Disruption of the MyD88 Gene Results in Loss of IL-1- and IL-18-Mediated Function
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Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations
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Self-citationBAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth
Schneider, P., MacKay, F., Steiner, V., Hofmann, K., Bodmer, J.-L., Holler, N., Ambrose, C., Lawton, P., Bixler, S., Acha-Orbea, H., et al. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.11.1747 · Cited by 1,333
Self-citationToll-like receptors in systemic autoimmune disease
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BAFF and APRIL: A Tutorial on B Cell Survival
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Self-citationType I Interferon in Systemic Lupus Erythematosus and Other Autoimmune Diseases
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(2006) · Elsevier eBooks · doi:10.1016/b978-0-12-595961-2.x5000-8 · Cited by 962
Cited by
Mackay, F., & Schneider, P. (2009) · Nature Reviews Immunology · doi:10.1038/nri2572 · Cited by 930
Self-citationB 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
Germinal Center and Extrafollicular B Cell Responses in Vaccination, Immunity, and Autoimmunity
Elsner, R. A., & Shlomchik, M. J. (2020) · Immunity · doi:10.1016/j.immuni.2020.11.006 · Cited by 526
Neuropsychiatric lupus: new mechanistic insights and future treatment directions
Schwartz, N., Stock, A. D., & Putterman, C. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-018-0156-8 · Cited by 429
Overexpression of the Cytokine BAFF and Autoimmunity Risk
Steri, M., Orrù, V., Idda, M. L., Pitzalis, M., Pala, M., Zara, I., Sidore, C., Faà, V., Floris, M., Deiana, M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1610528 · Cited by 382
Metadata
- Authors
- Groom, J. R., Fletcher, C. A., Walters, S. N., Grey, S. T., Watt, S. V., Sweet, M. J., Smyth, M. J., Mackay, C. R., & Mackay, F.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2007-07-30
- Volume
- 204
- Issue
- 8
- Pages
- 1959-1971
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2132773720
- Cited by
- 377
- References
- 64
- FWCI
- 17.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Groom, J. R., Fletcher, C. A., Walters, S. N., Grey, S. T., Watt, S. V., Sweet, M. J., Smyth, M. J., Mackay, C. R., & Mackay, F. (2007). BAFF and MyD88 signals promote a lupuslike disease independent of T cells. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20062567
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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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