Rheumatoid arthritis synovial stromal cells inhibit apoptosis and up-regulate Bcl-xL expression by B cells in a CD49/CD29-CD106-dependent mechanism
Rheumatoid arthritis synovial stromal cells inhibit apoptosis and up-regulate Bcl-xL expression by B cells in a CD49/CD29-CD106-dependent mechanism
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DOI：
10.4049/jimmunol.164.2.1110
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发表时间：
2000-01-15
影响因子：
4.4
通讯作者：
Lipsky, PE
中科院分区：
文献类型：
--
作者：
Hayashida, K;Shimaoka, Y;Lipsky, PE
炎症部位，如类风湿关节炎（RA）滑膜组织，含有大量活化的B细胞和浆细胞。然而，维持B细胞活力和促进其分化的机制尚不清楚，但与基质细胞的相互作用可能起作用。为了验证这一点，我们用取自RA滑膜组织的造口细胞系（SCL）培养纯化的人外周血B细胞，分析其对凋亡和bcl -2相关蛋白表达的影响。作为中心，B细胞也与骨关节炎滑膜或皮肤成纤维细胞的SCL一起培养，B细胞发生自发凋亡，然而，与RA SCL细胞一起培养的B细胞表现出较少的凋亡和更高的活力，尽管骨关节炎滑膜和皮肤成纤维细胞的SCL也能使B细胞免于凋亡，但它们的效果不如RA SCL，但RA SCL以接触依赖的方式显著增加了B细胞的Bcl-x(L)表达。而B细胞Bcl-2的表达不受影响。抗CD106 （VCAM-1）单克隆抗体可阻断RA SCL对B细胞凋亡的保护和上调Bcl-x(L)的作用，但对CD54 （ICAM-1）单克隆抗体不起作用。此外，B细胞表面的CD49d/CD29（非常晚期Ag-4）交联可使B细胞免于凋亡，并上调Bcl-x(L)的表达。这些结果表明，RA滑膜组织来源的SCL通过诱导Bcl-x(L)表达和阻断I细胞凋亡，以CD49d/(CD29- cd106)依赖的方式促进B细胞存活。
Inflammatory sites, such as rheumatoid arthritis (RA) synovial tissue, contain large numbers of activated B cells and plasma cells. However, the mechanisms maintaining B cell viability and promoting their differentiation are not known, but interactions with stromal cells may play a role. To examine this, purified human peripheral B cells were cultured with a stomal cell line (SCL) derived from RA synovial tissue, and the effects on apoptosis and expression of Bcl-2-related proteins were analyzed. As a central, B cells were also cultured with SCL from osteoarthritis synovium or skin fibroblasts, B cells cultured with medium alone underwent spontaneous apoptosis, However, B cells cultured with RA SCL cells exhibited less apoptosis and greater viability, Although SCL from osteoarthritis synovium and skin fibroblasts also rescued B cells from apoptosis, they were less effective than RA SCL, B cell expression of Bcl-x(L) was markedly increased by RA SCL in a contact-dependent manner, whereas B cell expression of Bcl-2 was unaffected. Protection of B cells from apoptosis and up-regulation of Bcl-x(L) by RA SCL were both blocked by mAbs to CD106 (VCAM-1), but not CD54 (ICAM-1). Furthermore, cross-linking of CD49d/CD29 (very late Ag-4) on the surface of B cells rescued them from apoptosis and up-regulated Bcl-x(L) expression, These results indicate that SCL derived from RA synovial tissue play a role in promoting B cell survival by inducing Bcl-x(L) expression and blocking I) cell apoptosis in a CD49d/(CD29-CD106-dependent manner.