Activation process of mature B cell is predominantly driven by specific BCR-mediated pathways, switched on and off all through late B cell differentiation stages. Mice deficient for APS, a member of the Lnk/SH2B family of adaptor proteins, showed that this adaptor plays a BCR-mediated regulatory role in mature B cells. However, the intermediates involved in this adaptor modulating functions in B cells are still unknown. In the present study, we investigated the role of APS in regulating BCR signalling notably through cytoskeleton remodeling in mature B cells. Herein, we showed that APS function is stage specific, as it exclusively intervenes in mature B cells. Upon activation, APS colocalizes with the BCR and associates with important regulators of BCR signalling, such as Syk and Cbl kinase. Importantly, APS interferes, as a scaffold protein, with the stability of Syk kinase by recruiting Cbl. This function is mainly mediated by APS SH2 domain, which regulates BCR-evoked cell dynamics. Our findings thus reveal that APS plays a regulatory role in BCR-induced responses by specifically modulating its interacting partners, which positions APS as a relevant modulator of BCR signalling in mature B cells.

成熟 B 细胞的激活过程主要由特定的 BCR 介导的途径驱动，在整个 B 细胞分化晚期阶段开启和关闭。缺乏 APS（接头蛋白 Lnk/SH2B 家族成员）的小鼠表明，该接头在成熟 B 细胞中发挥 BCR 介导的调节作用。然而，参与该适配器在 B 细胞中调节功能的中间体仍然未知。在本研究中，我们研究了 APS 在调节 BCR 信号传导中的作用，特别是通过成熟 B 细胞中的细胞骨架重塑。在这里，我们表明 APS 功能是阶段特异性的，因为它专门干预成熟的 B 细胞。激活后，APS 与 BCR 共定位并与 BCR 信号传导的重要调节因子相关联，例如 Syk 和 Cbl 激酶。重要的是，APS 作为支架蛋白会干扰 通过招募 Cbl 具有 Syk 激酶的稳定性。该功能主要由 APS SH2 结构域介导，该结构域调节 BCR 诱发的细胞动力学。因此，我们的研究结果表明，APS 通过特异性调节其相互作用的伙伴，在 BCR 诱导的反应中发挥调节作用，这将 APS 定位为成熟 B 细胞中 BCR 信号传导的相关调节剂。