B cell tolerance and positive selection in lupus.

B cell tolerance and positive selection in lupus.
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DOI:
10.4049/jimmunol.1200848
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发表时间:
2012-07-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Wabl M
Wabl M
中科院分区:
其他
文献类型:
--
作者:
Eilat D;Wabl M

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系统性红斑狼疮 (SLE) 被认为是系统性自身免疫性疾病的原型;然而,尽管近年来在免疫学基本机制的理解方面取得了相当大的进展,但在阐明这种疾病的病因和发病机制方面却进展甚微。这甚至适用于近交系小鼠,例如易患狼疮的新西兰黑/新西兰白 (NZB/NZW) F1 小鼠,这些小鼠都经过基因编程,会在预定的年龄患上狼疮。这种令人沮丧的事态要求我们的科学思维发生根本性的改变,并为狼疮研究开辟新的方向。在此,我们认为,在易患狼疮的小鼠中,内在的 B 细胞耐受机制并未严重受损,但异常强烈的正选择事件会将少量自身反应性 B 细胞招募到生发中心。易感动物体细胞变化产生的核酸-蛋白质复合物可能会促进这一事件。
Systemic lupus erythematosus (SLE) is considered a prototype of systemic autoimmune diseases; however, despite considerable advances in recent years in the understanding of basic mechanisms in immunology, little progress has been made in elucidating the etiology and pathogenesis of this disease. This even holds for inbred mice, such as the lupus-prone New Zealand Black/New Zealand White (NZB/NZW) F1 mice, which are all genetically programmed to develop lupus at a predetermined age. This frustrating state of affairs calls for a fundamental change in our scientific thinking, and the opening of new directions in lupus research. Here, we suggest that intrinsic B cell tolerance mechanisms are not grossly impaired in lupus-prone mice, but that an unusually strong positive selection event recruits a small number of autoreactive B cells to the germinal centers. This event could be facilitated by nucleic acid–protein complexes that are created by somatic changes in the susceptible animal.
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