Jonathan Lagos, Ursula Holder, Sara Sagadiev, Andrea Montiel-Armendariz, Lucy Z. Li, Chandrashekhar Pasare, Baidong Hou, Jessica A. Hamerman, Mridu Acharya
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引用次数: 0
摘要
PI 3-激酶的 B 细胞适配器(BCAP)是一种与通过包括 B 细胞受体(BCR)在内的多种免疫受体发出信号有关的适配器分子。然而,BCAP 在抗体反应中的 B 细胞内在作用尚不清楚。我们研究了 BCAP 在 B 细胞对病毒颗粒的反应中的作用,发现了 BCAP 调节抗原特异性反应的一种以前未发现的机制。小鼠B细胞特异性缺失BCAP会导致BCR-抗原内吞缺陷,从而降低抗原特异性反应。BCAP 是协调抗原周围肌动蛋白重组的必要条件,以便通过 BCR 进行有效的内吞,并在细胞内处理抗原。因此,B细胞中 BCAP 的缺失会导致抗原内吞缺陷,阻碍抗原衍生信号的传播,降低 B 细胞向 T 细胞展示抗原的能力。因此,我们的研究阐明了 BCAP 如何调节 B 细胞对复杂抗原的反应,并阐明了 B 细胞内的抗原定位决定了 B 细胞活化的不同结果。
B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor
B cell adapter for PI 3-kinase (BCAP) is an adaptor molecule associated with signaling through multiple immune receptors, including the B cell receptor (BCR). However, B cell–intrinsic role of BCAP in antibody responses is unclear. We investigated the role of BCAP in B cell response to viral particles and found a previously unidentified mechanism by which BCAP regulates antigen-specific responses. B cell–specific deletion of BCAP in mice leads to decreases in antigen-specific responses through defects in BCR-antigen endocytosis. BCAP is necessary to orchestrate actin reorganization around the antigen for efficient endocytosis through BCR and intracellular processing of antigens. Therefore, loss of BCAP from B cells leads to defects in antigen endocytosis, hampering the propagation of antigen-derived signals and decreasing the ability of B cells to present antigens to T cells. Thus, our study clarifies how BCAP regulates B cell responses to complex antigens and elucidates that antigen positioning inside B cells determines different B cell activation outcomes.
期刊介绍:
Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.