Vora Kalpit A, Nichols Elizabeth, Porter Gene, Cui Yan, Keohane Carol Ann, Hajdu Richard, Hale Jeffery, Neway William, Zaller Dennis, Mandala Suzanne
Department of Immunology, Merck Research Laboratories, 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA.
J Leukoc Biol. 2005 Aug;78(2):471-80. doi: 10.1189/jlb.0904487. Epub 2005 May 13.
FTY720 is an immunosuppressive agent that modulates lymphocyte trafficking. It is phosphorylated in vivo to FTY720-phosphate (FTY-P) and binds to a family of G protein-coupled receptors recognizing sphingosine 1-phosphate (S1P) as the natural ligand. It has previously been reported that FTY-P blocks egress of lymphocytes from the thymus and lymph nodes, resulting in peripheral blood lymphopenia. We now report that FTY-P also causes displacement of marginal zone (MZ) B cells to the splenic follicles, an effect that is similar to that observed after in vivo administration of lipopolysaccharide. This effect is specific to B cells in the MZ, as treatment with FTY-P does not cause redistribution of the resident macrophage population. A small but statistically significant decrease in the expression of beta1 integrin on MZ B cells was observed with FTY-P treatment. The redistribution of MZ B cells from the MZ sinuses does not abolish the ability of these cells to respond to the T-independent antigen, trinitrophenol-Ficoll. It has been proposed that the displacement of MZ B cells to the follicles is an indication of cell activation. Consistent with this, FTY-P caused an increase in percentage of MZ B cells expressing activation markers CD9, CD1d, and CD24. These results suggest that S1P receptors on MZ B cells are responsible for their mobilization to follicles.
FTY720是一种调节淋巴细胞迁移的免疫抑制剂。它在体内磷酸化为磷酸化FTY720（FTY-P），并与一类识别1-磷酸鞘氨醇（S1P）作为天然配体的G蛋白偶联受体结合。此前有报道称，FTY-P可阻止淋巴细胞从胸腺和淋巴结流出，导致外周血淋巴细胞减少。我们现在报告，FTY-P还会使边缘区（MZ）B细胞向脾滤泡移位，这一效应与体内注射脂多糖后观察到的效应相似。这种效应是MZ中B细胞所特有的，因为用FTY-P处理不会导致驻留巨噬细胞群体的重新分布。用FTY-P处理后，观察到MZ B细胞上β1整合素的表达有轻微但具有统计学意义的下降。MZ B细胞从MZ窦的重新分布并没有消除这些细胞对非T细胞依赖性抗原三硝基苯酚-菲可的反应能力。有人提出，MZ B细胞向滤泡的移位是细胞活化的一个指标。与此一致的是，FTY-P导致表达活化标记CD9、CD1d和CD24的MZ B细胞百分比增加。这些结果表明，MZ B细胞上的S1P受体负责它们向滤泡的迁移。
