TLR9 drives the development of transitional B cells towards the marginal zone pathway and promotes autoimmunity
TLR9 drives the development of transitional B cells towards the marginal zone pathway and promotes autoimmunity
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DOI：
10.1016/j.jaut.2012.05.012
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发表时间：
2012-09-01
影响因子：
12.8
通讯作者：
Jamin, Christophe
中科院分区：
文献类型：
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作者：
Guerrier, Thomas;Youinou, Pierre;Jamin, Christophe
B细胞的成熟依赖于环境刺激。当抗原刺激与T细胞信号结合时，外周未成熟B细胞发育成滤泡途径。在这里，我们希望确定刺激有助于发展成边缘区B细胞已知参与自身免疫反应。我们发现TLR 9刺激过渡型B细胞诱导。增殖和特异性成熟为边缘区B细胞的特征性CD 24（-）CD 38（+）CD 21（高）CD 23（低）IgM（高）IgD（低）和Notch 2（高）B细胞。终末分化为与同种型转换定型相关的抗体分泌细胞也被触发，这导致自身抗体的显著产生。有趣的是，成熟的B细胞在TLR 9刺激后不分化成边缘区途径，过渡性B细胞在抗原和T细胞组合信号下也不分化成边缘区途径。这些结果表明，过渡B细胞是特别敏感的TLR 9刺激产生自身反应性边缘区B细胞。(C)2012爱思唯尔有限公司保留所有权利。
Maturation of B cells depends on environmental stimuli. Peripheral immature B cells develop into follicular pathway when antigenic stimulation is combined with T cell signals. Here, we wished to identify stimuli contributing to the development into marginal zone B cells known to be involved in autoimmune response. We found that TLR9 stimulation of transitional B cells induces. proliferation and specific maturation into CD24(-) CD38(+) CD21(high) CD23(low) IgM(high) IgD(low) and Notch2(high) B cells characteristics of marginal zone B cells. Terminal differentiation into antibody-secreting cell associated with isotype switch commitment is also triggered which leads to a striking production of autoantibodies. Interestingly, mature B cells do not differentiate into marginal zone pathway following TLR9 stimulation, nor do transitional B cells under antigenic and T cell combined signals. These results suggest that transitional B cells are specifically sensitive to TLR9 stimulation to produce autoreactive marginal zone B cells. (C) 2012 Elsevier Ltd. All rights reserved.