Aydar Yüksel, Balogh Péter, Tew John G, Szakal Andras K
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA 23298, USA.
Eur J Immunol. 2002 Oct;32(10):2817-26. doi: 10.1002/1521-4141(2002010)32:10<2817::AID-IMMU2817>3.0.CO;2-Z.
Morphological and kinetic studies of immune complex (IC) trapping by follicular dendritic cells (FDC) show marked age-related deficits. We postulated that a reduction in trapped IC, which generate CD21 ligands (L) on FDC, would lead to inadequate FDC-Ag-B cell interactions resulting in depressed Ab responses. To determine whether the age-related defect was the result of the aging of FDC or changes in the in vivo microenvironment of FDC (i.e. aging B and T cells), FDC-B cell-T cell-Ag interactions were studied in in vitro germinal centers where various combinations of old and young cells could be compared. Since we reasoned that reduced IC on FDC would generate less CD21L needed to stimulate the B cell co-receptor via CD21, we also examined the role of complement (C'). The hypothesis that aging reduces the accessory activity of FDC was tested with increasing numbers of FDC from young (12 weeks) or old (20 months) mice in the presence of young (12 weeks) B and T lymphocytes. The Ag-specific stimulatory activity of FDC was studied using the OVA-specific Ab response which was reduced by 40-50% in the presence of old FDC. Antigen-independent FDC-mediated co-stimulation was studied by using LPS to stimulate B-lymphocytes to produce immunoglobulin (Ig). In the presence of old FDC, co-stimulation was decreased by 70-80% in the LPS system. Incubation of aged FDC with IC and C' to provide FDC with CD21L restored co-stimulatory activity to near normal levels. In marked contrast, no defects in old B and T cells were apparent. The data suggest that the Ag handling capacity and co-stimulatory activity of old FDC become defective with aging and this appears to be a consequence of reduced trapping and presentation FDC-Ag and CD21L to B cells.
对滤泡树突状细胞（FDC）捕获免疫复合物（IC）的形态学和动力学研究显示出明显的年龄相关缺陷。我们推测，捕获的IC减少会导致FDC上CD21配体（L）生成减少，进而导致FDC-抗原-B细胞相互作用不足，从而使抗体反应受到抑制。为了确定年龄相关缺陷是FDC衰老还是FDC体内微环境变化（即B细胞和T细胞衰老）的结果，我们在体外生发中心研究了FDC-B细胞-T细胞-抗原相互作用，在该环境中可以比较不同组合的老年和年轻细胞。由于我们推断FDC上减少的IC会产生较少的CD21L，而CD21L是通过CD21刺激B细胞共受体所必需的，因此我们还研究了补体（C'）的作用。我们通过在年轻（12周）B淋巴细胞和T淋巴细胞存在的情况下，增加来自年轻（12周）或老年（20个月）小鼠的FDC数量，来验证衰老会降低FDC辅助活性这一假设。使用卵清蛋白（OVA）特异性抗体反应研究FDC的抗原特异性刺激活性，在存在老年FDC的情况下，该反应降低了40%-50%。通过使用脂多糖（LPS）刺激B淋巴细胞产生免疫球蛋白（Ig），研究了抗原非依赖性FDC介导的共刺激作用。在LPS系统中，存在老年FDC时，共刺激作用降低了70%-80%。用IC和C'孵育老年FDC，为FDC提供CD21L，可使共刺激活性恢复到接近正常水平。与之形成鲜明对比的是，老年B细胞和T细胞没有明显缺陷。数据表明，老年FDC的抗原处理能力和共刺激活性会随着衰老而出现缺陷，这似乎是由于FDC向B细胞捕获和呈递FDC-抗原及CD21L减少所致。
