Al-Alwan Monther, Du Qiujiang, Hou Sen, Nashed Baher, Fan Yijun, Yang Xi, Marshall Aaron J
Department of Immunology, University of Manitoba, 703 William Avenue, Winnipeg, Manitoba, Canada.
J Immunol. 2007 Jun 15;178(12):7859-67. doi: 10.4049/jimmunol.178.12.7859.
We previously identified follicular dendritic cell secreted protein (FDC-SP), a small secreted protein of unknown function expressed in human tonsillar germinal centers (GC). To assess potential in vivo activities of FDC-SP, transgenic mice were generated to constitutively express FDC-SP in lymphoid tissues. FDC-SP transgenic mice show relatively normal development of immune cell populations, with the exception of a small increase in mature follicular B cells, and normal lymphoid tissue architecture. Upon immunization with a T-dependent Ag, FDC-SP transgenic mice were capable of producing an Ag-specific Ab; however, the titers of Ag-specific IgG2a and IgE were significantly reduced. GC responses after immunization were markedly diminished, with transgenic mice showing decreased numbers and sizes of GCs but normal development of follicular dendritic cell networks and normal positioning of GCs. FDC-SP transgenic mice also showed reduced production of Ag-specific IgG3 Ab after immunization with a type II T-independent Ag, suggesting that the FDC-SP can also regulate the induction of B cell responses outside the GC. Purified FDC-SP transgenic B cells function normally in vitro, with the exception of blunted chemotaxis responses to CXCL12 and CXCL13. FDC-SP can induce the chemotaxis of CD40-stimulated nontransgenic B cells and can significantly enhance B cell migration in combination with chemokines, indicating that FDC-SP may function in part by regulating B cell chemotaxis. These results provide the first evidence for immunomodulatory activities of FDC-SP and implicate this molecule as a regulator of B cell responses.
我们之前鉴定出了滤泡树突状细胞分泌蛋白（FDC-SP），这是一种在人类扁桃体生发中心（GC）表达的功能未知的小分泌蛋白。为了评估FDC-SP在体内的潜在活性，构建了转基因小鼠，使其在淋巴组织中组成性表达FDC-SP。FDC-SP转基因小鼠的免疫细胞群体发育相对正常，只是成熟滤泡B细胞略有增加，且淋巴组织结构正常。在用胸腺依赖性抗原免疫后，FDC-SP转基因小鼠能够产生抗原特异性抗体；然而，抗原特异性IgG2a和IgE的滴度显著降低。免疫后的GC反应明显减弱，转基因小鼠的GC数量和大小减少，但滤泡树突状细胞网络发育正常，GC定位正常。在用II型非胸腺依赖性抗原免疫后，FDC-SP转基因小鼠的抗原特异性IgG3抗体产生也减少，这表明FDC-SP也可以调节GC外B细胞反应的诱导。纯化的FDC-SP转基因B细胞在体外功能正常，但对CXCL12和CXCL13的趋化反应减弱。FDC-SP可以诱导CD40刺激的非转基因B细胞的趋化作用，并能与趋化因子联合显著增强B细胞迁移，这表明FDC-SP可能部分通过调节B细胞趋化作用发挥功能。这些结果为FDC-SP的免疫调节活性提供了首个证据，并表明该分子是B细胞反应的调节因子。
