Intrinsic properties of immunoglobulin IgG1 isotype-switched B cell receptors promote microclustering and the initiation of signaling.

Intrinsic properties of immunoglobulin IgG1 isotype-switched B cell receptors promote microclustering and the initiation of signaling.
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DOI:
10.1016/j.immuni.2010.06.006
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发表时间:
2010-06-25
期刊:
影响因子:
32.4
通讯作者:
Pierce SK
Pierce SK
中科院分区:
医学1区
文献类型:
--
作者:
Liu W;Meckel T;Tolar P;Sohn HW;Pierce SK

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记忆B细胞表达高亲和力的免疫球蛋白B细胞受体(Ig G-BCR),增强B细胞的反应,导致快速产生高亲和力的Ig G抗体。尽管Ig G-BCRs在记忆反应中起着中心作用,但Ig G-BCRs增强B细胞反应的机制尚不完全清楚。利用高分辨率活细胞成像,我们发现,与亲和力无关,IgG1-BCR显著增强了B细胞与膜结合抗原相遇后几秒钟内最早的BCR内源性事件,包括BCR寡聚和BCR微簇生长,导致Syk激酶募集和钙反应。这些早期事件的增强依赖于IgG1细胞质尾部的膜近端区域,以前未被认为在IgG1-bcr信号中发挥作用。因此,IgG1-BCR的固有特性增强了早期的抗原驱动事件,最终转化为增强的信号。
Memory B cells express high affinity, immunoglobulin B cell receptors (IgG-BCRs) that enhance B cell responses giving rise to the rapid production of high affinity, IgG antibodies. Despite the central role of IgG-BCRs in memory responses, the mechanisms by which the IgG-BCRs function to enhance B cell responses are not fully understood. Using high-resolution live-cell imaging we showed that independent of affinity, IgG1-BCRs dramatically enhanced the earliest BCR-intrinsic events that followed within seconds of B cells’ encounter with membrane bound antigen including BCR oligomerization and BCR microcluster growth, leading to Syk kinase recruitment and calcium responses. The enhancement of these early events was dependent on a membrane proximal region of the IgG1 cytoplasmic tail not previously appreciated to play a role in IgG1-BCR signaling. Thus, intrinsic properties of the IgG1-BCR enhance early antigen-driven events that ultimately translate into heightened signaling.
DOI: 10.1083/jcb.200802007
发表时间: 2008-07-28
期刊: The Journal of cell biology
影响因子: --
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