Department of Microbiology & Immunology, I(3) and CELL Research Groups, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Cell Immunol. 2012 Jan-Feb;275(1-2):47-54. doi: 10.1016/j.cellimm.2012.03.002. Epub 2012 Mar 29.
B-lymphocytes produce protective antibodies but also contribute to autoimmunity. In particular, marginal zone (MZ) B cells recognize both microbial components and self-antigens. B cell trafficking is critical for B cell activation and is controlled by chemoattactants such as CXCL13 and sphingosine 1-phosphate (S1P). The related tyrosine kinases focal adhesion kinase (FAK) and proline-rich tyrosine kinase (Pyk2) regulate cell migration and adhesion but their roles in B cells are not fully understood. Using a novel Pyk2-selective inhibitor described herein (PF-719), as well as a FAK-selective inhibitor, we show that both Pyk2 and FAK are important for CXCL13- and S1P-induced migration of B-2 cells and MZ B cells. In contrast, LFA-1-mediated adhesion required only Pyk2 whereas activation of the Akt pro-survival kinase required FAK but not Pyk2. Thus Pyk2 and FAK mediate critical processes in B cells and these inhibitors can be used to further elucidate their functions in B cells.
B 淋巴细胞产生保护性抗体，但也有助于自身免疫。特别是边缘区（MZ）B 细胞可识别微生物成分和自身抗原。B 细胞的迁移对于 B 细胞的激活至关重要，并且受到趋化因子（如 CXCL13 和鞘氨醇 1-磷酸（S1P））的控制。相关的酪氨酸激酶粘着斑激酶（FAK）和富含脯氨酸的酪氨酸激酶（Pyk2）调节细胞迁移和黏附，但它们在 B 细胞中的作用尚未完全阐明。使用本文描述的新型 Pyk2 选择性抑制剂（PF-719）以及 FAK 选择性抑制剂，我们表明 Pyk2 和 FAK 对于 B-2 细胞和 MZ B 细胞中 CXCL13 和 S1P 诱导的迁移均很重要。相比之下，LFA-1 介导的黏附仅需要 Pyk2，而 Akt 生存促进激酶的激活需要 FAK，但不需要 Pyk2。因此，Pyk2 和 FAK 介导 B 细胞中的关键过程，并且这些抑制剂可用于进一步阐明它们在 B 细胞中的功能。
