Signalinginto Lipid Rafts Reveals a Novel Step in Translocation of the B Cell Antigen Receptor
Signalinginto Lipid Rafts Reveals a Novel Step in Translocation of the B Cell Antigen Receptor
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发表时间：
2001
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通讯作者：
P. Cheng;B. Brown;Wenxia Song;S. Pierce
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作者：
P. Cheng;B. Brown;Wenxia Song;S. Pierce
B细胞Ag受体（BCR）的交联导致信号转导级联的启动，其中最早的事件涉及Src家族激酶Lyn磷酸化免疫受体酪氨酸为基础的Ig a和Ig B激活基元，以及BCR与肌动蛋白细胞骨架的关联。然而，BCR交联启动级联的机制仍然不清楚。本研究利用多种a20转染细胞系，提供了生化和遗传证据，证明BCR交联可导致BCR易位为富含胆固醇和鞘脂的脂筏，这一过程不依赖于BCR信号的启动，也不需要肌动蛋白细胞骨架。BCR转运到脂质筏中不需要Ig a /Ig b信号复合物，不依赖于FcR的参与，也不被Src家族激酶抑制剂PP2或肌动蛋白解聚剂细胞松弛素D或latrunculin阻断。因此，BCR的交联或寡聚化诱导BCR易位到脂筏中，定义了B细胞激活中的一个事件，该事件先于受体磷酸化并与肌动蛋白细胞骨架相关。中华免疫学杂志，2001,16(6):393 - 391。
The cross-linking of the B cell Ag receptor (BCR) leads to the initiation of a signal transduction cascade in which the earliest events involve the phosphorylation of the immunoreceptor tyrosine-based activation motifs of Ig a and Ig b by the Src family kinase Lyn and association of the BCR with the actin cytoskeleton. However, the mechanism by which BCR cross-linking initiates the cascade remains obscure. In this study, using various A20-transfected cell lines, biochemical and genetic evidence is provided that BCR cross-linking leads to the translocation of the BCR into cholesterol- and sphingolipid-rich lipid rafts in a process that is independent of the initiation of BCR signaling and does not require the actin cytoskeleton. Translocation of the BCR into lipid rafts did not require the Ig a /Ig b signaling complex, was not dependent on engagement of the FcR, and was not blocked by the Src family kinase inhibitor PP2 or the actin-depolymerizing agents cytochalasin D or latrunculin. Thus, cross-linking or oligomerization of the BCR induces the BCR translocation into lipid rafts, defining an event in B cell activation that precedes receptor phosphorylation and association with the actin cytoskeleton. The Journal of Immunology, 2001, 166: 3693–3701.