Sphingosine-1-Phosphate Receptors in Human B Cells: Expression, Role and Signaling

人类 B 细胞中的 1-磷酸鞘氨醇受体：表达、作用和信号转导

• 批准号: 39297849
• 负责人: Professor Dr. Hermann Eibel
• 金额: --
• 依托单位: Centrum für Chronische Immundefizienz (CCI)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/39297849?language=en
• 关键词: Sphingosine; Phosphate; Receptors; Human; Cells

Studying the functions of sphingosine-1 phosphate (S1P) in human B cells we hope to contribute to the understanding of human B cell malignancies and to provide new tools and procedures for diagnosis, staging and treatment. Using primary human B cells, samples from B cell malignancies, human B cell lines, and humanized mouse models, we examine how S1P receptors elicit and modulate cellular responses to S1P, interfere with signals that regulate human B cell development, growth and differentiation. By comparing normal and malignant B cells we hope that we can characterize how S1P-dependent pathways contribute to lymphomagenesis. Fusion proteins between S1P receptors and fluorescence proteins like GFP are introduced into human B cell lines by lentiviral gene transfer to analyze the S1P receptor response to S1P binding, receptor internalization and compartmentalization in living cells. The results should reveal the functional differences between S1P receptors in B cells, define the critical residues and domains within the receptors and provide insight into the interactions between signals induced by S1P and essential B-lymphocyte specific receptors. Since new therapeutic approaches are based on the application of S1P analoga the projected outcome should help in understanding the beneficial and adverse effects of these therapies.

研究鞘氨醇-1磷酸(S1P)在人类B细胞中的功能，希望有助于对人类B细胞恶性肿瘤的认识，并为诊断、分期和治疗提供新的工具和程序。使用原代人类B细胞、来自B细胞恶性肿瘤的样本、人类B细胞系和人源化小鼠模型，我们研究了S1P受体如何诱导和调节细胞对S1P的反应，干扰调节人类B细胞发育、生长和分化的信号。通过对正常和恶性B细胞的比较，我们希望我们能够表征S1P依赖的通路如何促进淋巴肿大。通过慢病毒基因转移将S1P受体与GFP等荧光蛋白之间的融合蛋白导入人B细胞系，分析活细胞中S1P受体对S1P结合、受体内化和区域化的反应。这些结果将揭示B细胞中S1P受体之间的功能差异，确定受体内的关键残基和结构域，并为深入了解S1P诱导的信号与必要的B淋巴细胞特异性受体之间的相互作用提供依据。由于新的治疗方法是基于S1P类似物的应用，预测的结果应该有助于理解这些治疗的益处和不良影响。