Early Events of B Cell Activation by Antigen
Early Events of B Cell Activation by Antigen
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DOI：
10.1126/scisignal.263pt1
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发表时间：
2009-03-24
影响因子：
7.3
通讯作者：
Batista, Facundo D.
中科院分区：
文献类型：
--
作者：
Depoil, David;Weber, Michele;Batista, Facundo D.
B细胞的激活通过产生产生高亲和力抗体和记忆细胞的浆细胞，提供了对过多传染病的长期保护。B细胞受体(BCR)与同源抗原结合，启动细胞内信号传递和随后的抗原内化。膜结合抗原现在被认为是在体内启动B细胞活化的主要形式。我们已经证明，在识别提呈细胞表面的抗原后，B细胞在形态上经历了戏剧性的变化，其特征是快速扩散，随后沿着提呈表面更长时间地收缩。这种两相反应增加了B细胞积累、内化并随后呈递给T细胞的抗原量。因此，扩张和收缩反应决定了B细胞激活的结果。我们使用平面脂质双层和全内反射荧光显微镜相结合的方法来研究在BCR结合之后和B细胞扩散之前发生的早期事件。我们观察到BCR抗原微团的迅速形成，我们将其重新定义为“微信号小体”，因为它们介导了细胞内效应物的协调募集，如激酶Lyn和Syk、接头Vav和磷脂酶C-Gamma 2(PLC-Gamma 2)。我们确定了辅助受体CD19在调节B细胞对膜结合抗原的反应中的扩散和激活中的重要作用。初步证据表明，体外描述的细胞形态变化很可能发生在体内对淋巴结巨噬细胞表面抗原的识别上。
The activation of B cells confers long-lasting protection from a plethora of infectious diseases through the generation of plasma cells that produce high-affinity antibodies and memory cells. Engagement of the B cell receptor (BCR) with cognate antigen initiates intracellular signaling and subsequent internalization of antigen. Membrane-bound antigens are now considered the predominant forms that initiate B cell activation in vivo. We have shown that upon recognition of antigen on the surface of a presenting cell, the B cell undergoes a dramatic change in morphology characterized by rapid spreading followed by more prolonged contraction along the presenting surface. This two-phase response increases the amount of antigen that the B cell accumulates, internalizes, and subsequently presents to T cells. Thus, the spreading and contraction response shapes the outcome of B cell activation. We used a combination of planar lipid bilayers and total internal reflection fluorescence microscopy to investigate the early events that occur after engagement of the BCR and before B cell spreading. We observed the rapid formation of BCR-antigen microclusters, which we redefine as "microsignalosomes" because they mediate the coordinated recruitment of intracellular effectors, such as the kinases Lyn and Syk, the adaptor Vav, and phospholipase C-gamma 2 (PLC-gamma 2). We identified an essential role for the co-receptor CD19 in mediating spreading, and thus B cell activation, in response to membrane-bound antigen. Preliminary evidence suggests that the cellular morphology changes described in vitro are likely to occur upon recognition of antigen presented on the surface of macrophages in lymph nodes in vivo.