Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation
Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation
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DOI：
10.1016/j.immuni.2007.12.003
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发表时间：
2008-01-01
期刊：
影响因子：
32.4
通讯作者：
Batista, Facundo D.
中科院分区：
文献类型：
--
作者：
Arana, Eloisa;Vehlow, Anne;Batista, Facundo D.
整合素白细胞功能相关抗原-1 （LFA-1）在促进B细胞粘附中起重要作用，从而促进免疫突触（is）的形成和B细胞的活化。尽管具有这一意义，调控LFA-1激活的相关信号机制仍然难以捉摸。在这里，我们发现原代B细胞表达的小GTPase Rac的两种亚型，Rac1和Rac2，在BCR参与后，在src家族激酶、鸟嘌呤核苷酸交换因子Vav1和Vav2以及磷酸肌醇-3激酶（PI3K）的下游被迅速激活。我们发现Rac2，而不是Rac1，在B细胞粘附细胞间粘附分子-1 （ICAM-1）和IS形成中起关键作用。此外，表达本构活性Rac2的B细胞具有很强的粘附性。我们观察到，缺乏rac2的B细胞表现出较低数量的Rap1-GTP和严重的肌动蛋白聚合缺陷，确定了其行为背后的潜在机制。我们假设Rac2在介导B细胞粘附和IS形成中的关键作用可能适用于所有淋巴细胞。
The integrin leukocyte function-associated antigen-1 (LFA-1) is important in the promotion of B cell adhesion, thereby facilitating immunological synapse (IS) formation and B cell activation. Despite this significance, the associated signaling mechanisms regulating LFA-1 activation remain elusive. Here, we show that both isoforms of the small GTPase Rac expressed by primary B cells, Rac1 and Rac2, were activated rapidly downstream of Src-family kinases, guanine-nucleotide exchange factors Vav1 and Vav2, and phosphoinositide-3 kinase (PI3K) after BCR engagement. We identify Rac2, but not Rac1, as critical for B cell adhesion to intercellular adhesion molecule-1 (ICAM-1) and IS formation. Furthermore, B cells expressing constitutively active Rac2 are highly adhesive. We observe that Rac2-deficient B cells exhibit lower amounts of Rap1-GTP and severe actin polymerization defects, identifying a potential mechanism underlying their behavior. We postulate that this critical role for Rac2 in mediating B cell adhesion and IS formation might apply in all lymphocytes.