The Bacterial Enzyme IdeS Cleaves the IgG-Type of B Cell Receptor (BCR), Abolishes BCR-Mediated Cell Signaling, and Inhibits Memory B Cell Activation
The Bacterial Enzyme IdeS Cleaves the IgG-Type of B Cell Receptor (BCR), Abolishes BCR-Mediated Cell Signaling, and Inhibits Memory B Cell Activation
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DOI：
10.4049/jimmunol.1501929
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发表时间：
2015-12-15
影响因子：
4.4
通讯作者：
Kjellman, Christian
中科院分区：
文献类型：
--
作者：
Jarnum, Sofia;Bockermann, Robert;Kjellman, Christian
AG与BCR的结合是B细胞发育和激活的关键步骤，启动一系列信号事件，最终导致增殖、分化或细胞死亡。一种细菌酶，化脓性链球菌的免疫球蛋白降解酶(IDES)，能在可溶性免疫球蛋白的铰链区下特异性地裂解免疫球蛋白分子，当免疫球蛋白与抗原结合时，产生一个F(ab‘)2分子和一个同源二聚体Fc片段。目前尚不清楚IDES在与CD79a和CD79b形成的复合体中存在于附着在B细胞膜上的BCR中时，是否也能切割Ig G分子。在这篇文章中，我们介绍了体外和体外数据显示，IDES裂解存在于BCR复合体中的免疫球蛋白G，并非常有效地阻断与BCR的Ag结合。由于IDES裂解BCR，BCR下游的信号级联被阻断，记忆B细胞暂时沉默，阻止它们对抗原刺激做出反应，并将其转变为产生抗体的细胞。
Ag binding to the BCR is a critical step in B cell development and activation, initiating a cascade of signaling events ultimately leading to proliferation, differentiation, or cell death. A bacterial enzyme, IgG-degrading enzyme of Streptococcus pyogenes (IdeS), was shown to specifically cleave IgG molecules below the hinge region of soluble IgG and when IgG is bound to Ag, resulting in one F(ab')2 molecule and one homodimeric Fc fragment. Whether IdeS could also cleave the IgG molecule when it is present in the BCR attached to the B cell membrane in a complex with CD79a and CD79b is unknown. In this article, we present human in vitro and ex vivo data showing that IdeS cleaves the IgG present in the BCR complex and very efficiently blocks Ag binding to the BCR. As a consequence of IdeS cleaving the BCR, signaling cascades downstream of the BCR are blocked, and memory B cells are temporarily silenced, preventing them from responding to antigenic stimulation and their transition into Ab-producing cells.