Unique maturation program of the IgE response in vivo

Unique maturation program of the IgE response in vivo
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DOI:
10.1016/j.immuni.2006.12.006
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发表时间:
2007-02-01
期刊:
影响因子:
32.4
通讯作者:
Lafaille, Juan J.
Lafaille, Juan J.
中科院分区:
医学1区
文献类型:
--
作者:
Erazo, Agustin;Kutchukhidze, Nino;Lafaille, Juan J.

文献摘要

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哮喘和过敏发病机制中的一个关键事件是IgE抗体的产生。我们在此表明,IgE(+)细胞是特殊的,因为它们主要在生发中心之外被发现,并且从很早开始就表达浆细胞的基因程序。尽管它们位于生发中心之外,IgE(+)细胞仍显示出体细胞高频突变和亲和力成熟的迹象。我们证明,高亲和力IgE(+)细胞可通过一个独特的分化程序产生,该程序涉及两个阶段:一个是前IgE阶段,在此阶段体细胞高频突变和亲和力成熟发生在IgG1(+)细胞中;另一个是IgE转换后阶段,在此阶段IgE细胞迅速分化为浆细胞。我们的研究结果对理解过敏中IgE记忆反应具有重要意义。
A key event in the pathogenesis of asthma and allergies is the production of IgE antibodies. We show here that IgE(+) cells were exceptional because they were largely found outside germinal centers and expressed, from very early on, a genetic program of plasma cells. In spite of their extragerminal center localization, IgE(+) cells showed signs of somatic hypermutation and affinity maturation. We demonstrated that high-affinity IgE(+) cells could be generated through a unique differentiation program that involved two phases: a pre-IgE phase in which somatic hypermutation and affinity maturation take place in IgG1(+) cells, and a post-IgE-switching phase in which IgE cells differentiate swiftly into plasma cells. Our results have implications for the understanding of IgE memory responses in allergy.