Benet Zachary, Jing Zhixin, Fooksman David R
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cell Rep. 2021 Feb 9;34(6):108733. doi: 10.1016/j.celrep.2021.108733.
Using intravital imaging, we report that bone marrow (BM) plasma cells (PCs) are motile. BM PCs exhibit a unique migration pattern, characterized by intermittent periods of high motility and longer stretches of confined migration or arrest. BM PCs accumulate into clusters, which have reduced cell motility. APRIL promotes cluster formation and overall PC motility in the BM. Although CXCL12 and its receptor, CXCR4, promote PC motility in the BM, VLA4 activity promotes arrest. However, blocking either pathway promotes PC egress from the BM. Under steady-state conditions, BM PCs recirculate to other bones and spleen. In older mice, overall PC motility and recirculation increase, and this is correlated with increased CXCR4 expression, which depends on PC age or maturation rather than mouse age. Altogether, these results suggest that changes in PC motility and CXCR4 expression are linked with survival of long-lived PCs in the BM.
利用活体成像技术,我们发现骨髓(BM)浆细胞(PC)具有运动性。BM PC呈现出独特的迁移模式,其特征为间歇性的高运动期以及较长时间的受限迁移或静止期。BM PC聚集成簇,这些簇中的细胞运动性降低。增殖诱导配体(APRIL)促进BM中簇的形成以及整体PC的运动性。尽管CXC趋化因子配体12(CXCL12)及其受体CXC趋化因子受体4(CXCR4)促进BM中PC的运动性,但极迟抗原4(VLA4)活性促进静止。然而,阻断这两条途径中的任何一条都会促进PC从BM中逸出。在稳态条件下,BM PC会再循环至其他骨骼和脾脏。在老年小鼠中,整体PC的运动性和再循环增加,这与CXCR4表达增加相关,而CXCR4表达增加取决于PC的年龄或成熟度而非小鼠年龄。总之,这些结果表明PC运动性和CXCR4表达的变化与BM中长寿PC的存活相关。