Cheng P C, Brown B K, Song W, Pierce S K
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
J Immunol. 2001 Mar 15;166(6):3693-701. doi: 10.4049/jimmunol.166.6.3693.
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 alpha and Ig beta 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 alpha/Ig beta 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.
B细胞抗原受体（BCR）的交联引发信号转导级联反应，其中最早的事件包括Src家族激酶Lyn对Igα和Igβ基于免疫受体酪氨酸的激活基序进行磷酸化，以及BCR与肌动蛋白细胞骨架的结合。然而，BCR交联启动该级联反应的机制仍不清楚。在本研究中，利用各种转染了A20的细胞系，提供了生化和遗传学证据，表明BCR交联导致BCR在一个独立于BCR信号启动且不需要肌动蛋白细胞骨架的过程中转移到富含胆固醇和鞘脂的脂筏中。BCR向脂筏的转移不需要Igα/Igβ信号复合物，不依赖于FcR的结合，也不受Src家族激酶抑制剂PP2或肌动蛋白解聚剂细胞松弛素D或拉春库林的阻断。因此，BCR的交联或寡聚化诱导BCR转移到脂筏中，这确定了B细胞激活中先于受体磷酸化和与肌动蛋白细胞骨架结合的一个事件。
