Regulation of the B cell receptor repertoire and self-reactivity by BAFF.
Regulation of the B cell receptor repertoire and self-reactivity by BAFF.
复制标题
DOI：
10.4049/jimmunol.1002176
复制
发表时间：
2010-10-01
期刊：
影响因子：
--
通讯作者：
Nemazee D
中科院分区：
文献类型：
--
作者：
Ota M;Duong BH;Torkamani A;Doyle CM;Gavin AL;Ota T;Nemazee D
细胞因子BAFF促进B淋巴细胞存活，并在系统性红斑狼疮和Sjögren综合征患者中过度表达。BAFF可以拯救无能自身反应性B细胞免于死亡，但仅在缺乏非自身反应性B细胞竞争的情况下。然而，在拥有多种B细胞的个体中，高BAFF水平促进自身抗体的形成。为了更好地了解过量BAFF如何促进多克隆免疫系统中的自身免疫，我们分析了3H9位点定向高链转基因小鼠中igl链的使用情况，其B细胞在表达某些内源性l链时识别DNA和染色质。通过引入表达BAFF或其天然抑制剂ΔBAFF的转基因，在3H9小鼠中控制BAFF水平。BAFF/3H9小鼠的B细胞数量增加，使用广泛的l链库，包括产生高亲和力自身反应性的l链，并产生丰富的自身抗体。脾和淋巴结B细胞的比较表明，高自身反应性B细胞扩增。相比之下，ΔBAFF/3H9小鼠的B细胞数量减少，其库与3H9小鼠相似，但缺乏Vκ基因子集的使用。结果表明，限制BAFF信号选择针对高亲和力的自反应性B细胞，而其过表达导致广泛耐受逃逸和自反应性细胞的阳性选择。
The cytokine BAFF promotes B lymphocyte survival and is overexpressed in individuals with systemic lupus erythematosus and Sjögren’s Syndrome. BAFF can rescue anergic autoreactive B cells from death, but only when competition from nonautoreactive B cells is lacking. Yet high BAFF levels promote autoantibody formation in individuals possessing diverse B cells. To better understand how excess BAFF promotes autoimmunity in a polyclonal immune system, IgL-chain usage was analyzed in 3H9 site-directed IgH-chain transgenic mice, whose B cells recognize DNA and chromatin when they express certain endogenous L-chains. BAFF levels were manipulated in 3H9 mice by introducing transgenes expressing either BAFF or its natural inhibitor ΔBAFF. B cells in BAFF/3H9 mice were elevated in number, used a broad L-chain repertoire, including L-chains generating high affinity autoreactivity, and produced abundant autoantibodies. Comparison of spleen and lymph node B cells suggested that highly autoreactive B cells were expanded. By contrast, ΔBAFF/3H9 mice had reduced B cell numbers with a repertoire similar to that of 3H9 mice, but lacking usage of a subset of Vκ genes. The results suggest that limiting BAFF signaling selects against higher affinity autoreactive B cells, whereas its overexpression leads to broad tolerance escape and positive selection of autoreactive cells.
登录
查看更多内容
影响因子：
30.5
作者：
Fukuyama, H;Nimmerjahn, F;Ravetch, JV
通讯作者：
Ravetch, JV
影响因子：
4.9
作者：
Collins CE;Gavin AL;Migone TS;Hilbert DM;Nemazee D;Stohl W
通讯作者：
Stohl W
影响因子：
4.4
作者：
Kiefer, Kerstin;Nakajima, Pamela B.;Bosma, Melvin J.
通讯作者：
Bosma, Melvin J.
DOI：
10.1084/jem.177.4.999
发表时间：
1993-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gay D;Saunders T;Camper S;Weigert M
通讯作者：
Weigert M
影响因子：
32.4
作者：
Chen, C;Prak, EL;Weigert, M
通讯作者：
Weigert, M