Decision criteria for resolving isotype switching conflicts by B cells

Decision criteria for resolving isotype switching conflicts by B cells
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DOI:
10.1002/eji.200425719
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发表时间:
2005-10-01
影响因子:
5.4
通讯作者:
Hodgkin, PD
Hodgkin, PD
中科院分区:
医学3区
文献类型:
--
作者:
Deenick, EK;Hasbold, J;Hodgkin, PD

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B 细胞的同种型转换受到一组细胞因子的高度调节,包括 IL-4、IFN-γ 和 TGF-β。 B 细胞一次只能表达一种同种型;然而,在免疫反应过程中,它可能会受到刺激组合的影响,从而为其提供相互冲突的转换指令。为了确定如何解决这种细胞因子诱导的同型转换冲突,研究了暴露于多种细胞因子的 B 细胞的反应。为了消除转换细胞因子对增殖的同时影响而产生的并发症,使用分裂数作为监测转换率的参考框架。结果显示出明显的层次结构,其中 IFN-γ 优于 IL-4,并且 IL-4 和 IFN-γ 均优于 TGF-β。这些研究揭示了 B 细胞如何拥有一套逻辑决策标准来处理引起一系列不同刺激的病原体。
Isotype switching by B cells is highly regulated by a group of cytokines including IL-4, IFN-gamma and TGF-beta. A B cell can only express one isotype at a time; however during an, immune response it may be exposed to combinations of stimuli that provide it with conflicting switching instructions. To determine how such cytokine-induced isotype switch conflicts would be resolved, the responses of B cells exposed to multiple cytokines were investigated. To eliminate complications arising from simultaneous effects of switching cytokines on proliferation, division number was used as a reference framework to monitor switching rate. The results show a clear hierarchy in which IFN-gamma is dominant over IL-4, and both IL-4 and IFN-gamma are dominant over TGF-beta. These studies reveal how B cells possess a set of logical decision criteria for dealing with pathogens that invoke a range of different stimuli.