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B cell-intrinsic requirement for WNK1 kinase in T cell-dependent antibody responses
bioRxiv - Immunology Pub Date : 2021-09-09 , DOI: 10.1101/2021.09.09.459588
Darryl Hayward , Lesley Vanes , Stefanie Wissmann , Sujana Sivapatham , Harald Hartweger , Joshua Biggs O'May , Leon De Boer , Richard Mitter , Robert Kochl , Jens V Stein , Victor LJ Tybulewicz

Migration and adhesion play critical roles in B cells, regulating recirculation between lymphoid organs, migration within lymphoid tissue and interaction with CD4+ T cells. However, there is limited knowledge of how B cells integrate chemokine receptor and integrin signaling with B cell activation to generate efficient humoral responses. Here we show that the WNK1 kinase, a regulator of migration and adhesion, is essential in B cells for T-dependent antibody responses. We demonstrate that WNK1 transduces signals from the BCR, CXCR5 and CD40, and using intravital imaging we show that WNK1 regulates migration of naive and activated B cells, and their interactions with T cells. Unexpectedly, we show that WNK1 is required for BCR- and CD40-induced proliferation, acting through the OXSR1 and STK39 kinases, and for efficient B cell-T cell collaboration in vivo. Thus, WNK1 is critical for humoral immune responses, by regulating B cell migration, adhesion and T cell-dependent activation.

中文翻译:

T 细胞依赖性抗体反应中 WNK1 激酶的 B 细胞内在要求

迁移和粘附在 B 细胞中起着关键作用,调节淋巴器官之间的再循环、淋巴组织内的迁移以及与 CD4 + 的相互作用T细胞。然而,关于 B 细胞如何将趋化因子受体和整合素信号与 B 细胞活化结合以产生有效的体液反应的知识有限。在这里我们显示 WNK1 激酶,迁移和粘附的调节器,在 B 细胞中对于 T 依赖性抗体反应是必不可少的。我们证明 WNK1 转导来自 BCR、CXCR5 和 CD40 的信号,并使用活体成像显示 WNK1 调节幼稚和活化 B 细胞的迁移,以及它们与 T 细胞的相互作用。出乎意料的是,我们发现 WNK1 是 BCR 和 CD40 诱导的增殖所必需的,通过 OXSR1 和 STK39 激酶起作用,以及体内有效的 B 细胞-T 细胞协作. 因此,WNK1 通过调节 B 细胞迁移、粘附和 T 细胞依赖性激活对体液免疫反应至关重要。
更新日期:2021-09-12
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