Precursor B cells for autoantibody production in genomically Fas-intact autoimmune disease are not subject to Fas-mediated immune elimination
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- Sachiko Hirose
- Department of Pathology, Juntendo University School of Medicine, Tokyo 113, Japan
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- Kwangseok Yan
- Department of Pathology, Juntendo University School of Medicine, Tokyo 113, Japan
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- Masaaki Abe
- Department of Pathology, Juntendo University School of Medicine, Tokyo 113, Japan
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- Yi Jiang
- Department of Pathology, Juntendo University School of Medicine, Tokyo 113, Japan
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- Yoshitomo Hamano
- Department of Pathology, Juntendo University School of Medicine, Tokyo 113, Japan
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- Hiromichi Tsurui
- Department of Pathology, Juntendo University School of Medicine, Tokyo 113, Japan
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- Toshikazu Shirai
- Department of Pathology, Juntendo University School of Medicine, Tokyo 113, Japan
書誌事項
- 公開日
- 1997-08-19
- DOI
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- 10.1073/pnas.94.17.9291
- 公開者
- National Academy of Sciences
この論文をさがす
説明
<jats:p> The Fas/Fas ligand (FasL) system participates in regulation of the immune system through the apoptotic process. However, the extent to which abnormalities in this system are involved in the loss of self-tolerance and development of autoimmune disease not associated with Fas/FasL mutations remains unknown. The present study addresses this issue in Fas/FasL-intact, systemic lupus erythematosus (SLE)-prone (NZB × NZW) (NZB/W) F <jats:sub>1</jats:sub> mice. While splenic B cells from 2-month-old mice before overt SLE expressed Fas poorly, <jats:italic>in vitro</jats:italic> stimulation with an agonistic anti-CD40 mAb up-regulated their Fas expression, thus revealing the existence of two populations: one was Fas <jats:sup>high</jats:sup> and highly susceptible to anti-Fas mAb-induced apoptosis, and the other was Fas <jats:sup>low</jats:sup> and apoptosis-resistant. The Fas <jats:sup>low</jats:sup> cells were included in the CD5 <jats:sup>+</jats:sup> B cell subpopulation and contained most of the cells that produced IgM anti-DNA antibodies. The isotype of anti-DNA antibodies switches from IgM to IgG in NZB/W F <jats:sub>1</jats:sub> mice at ages beginning at about 6 months. These IgG anti-DNA antibodies were produced almost exclusively by a subpopulation of splenic B cells that spontaneously expressed low levels of Fas <jats:italic>in vivo</jats:italic> and were apoptosis-resistant. The findings indicate that precursor B cells for autoantibody production and presumably autoantibody-secreting cells in these mice are relatively resistant to Fas-mediated apoptosis, a finding supporting the concept that abnormalities of Fas-mediated apoptotic process are involved in the development of autoreactive B cells in Fas/FasL-intact autoimmune disease. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 94 (17), 9291-9295, 1997-08-19
National Academy of Sciences
