LIFETIME OF EFFECTOR B CELLS

效应 B 细胞的寿命

• 批准号: 8171693
• 负责人: Thomas Dorner
• 金额: $ 0.85万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171693
• 关键词: Age; Antibodies; Antigens; B-Lymphocytes; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA; Development; Elements; Ensure; Europe; Funding; Grant; Half-Life; Human; Human body; Immune; Immune system; Immunoglobulin-Secreting Cells; Infection; Institution; Isotopes; Longevity; Measures; Memory; Memory B-Lymphocyte; Play; Population; Protein Binding; Research; Research Personnel; Resources; Role; Sampling; Serum; Source; Staging; United States National Institutes of Health; Vaccination; Vaccines; accelerator mass spectrometry; base; cell type; fighting; in vivo; pathogen; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human body integrity is largely based on a healthy immune system fighting pathogens. One key feature of the immune system is expression of memory, i.e. maintaining the ability to fight a pathogen upon its re-encounter effectively, even after years of pathogen absence. Based on that, vaccinations can prevent from severe infections. In pathogen defense, proteins binding specifically to the pathogen (antibodies) play a vital role. Antibodies tag the pathogen thus cause highly efficient degradation of the pathogen by specialized immune cells or neutralize it. The physical half-life of antibodies is less than 4 weeks. By contrast, specific antibodies induced by vaccination or infection can be readily detected in human blood serum after decades of antigen absence (humoral memory). This suggests that serum antibody levels are regulated at the stage of antibodysecreting cells, and their specific precursors (memory B cells). For both cell types, longevity vs. continuous renewal is discussed as means to maintain the entire cell population and its composition, but both concepts were neither proven nor disproven physically. In this project, want to measure 14C content in the DNA of antibody-secreting cells and memory B cells obtained from donors exposed to elevated levels of atmospheric 14C in Europe during the 1960ies. Elevated levels of the 14C isotope can still be detected in cells being quiescent since then, revealing their age. 14C analysis will require accelerator mass spectrometry (AMS) ensuring a precise quantitation of very low levels of 14C from minimum DNA samples. In analogy to Spalding et al (Cell, Vol. 122, 133143, July 15, 2005), this analysis will determine the in vivo age of candidate subsets of antibody-secreting cells and memory B cells and prove or disprove longevity of these cells, arguing in favor or against B cell longevity as a key element of humoral memory. The expected results will define new requirements for the successful development of effective vaccines.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 人体的完整性很大程度上取决于对抗病原体的健康免疫系统。该产品的一个关键特点是 免疫系统是记忆的表达，即在再次遇到病原体时保持抵抗病原体的能力 即使在多年没有病原体的情况下，也能有效地发挥作用。基于此，接种疫苗可以预防严重的 感染。在病原体防御中，与病原体特异性结合的蛋白质（抗体）发挥着至关重要的作用。 抗体标记病原体，从而通过专门的免疫高效降解病原体 细胞或中和它。抗体的物理半衰期小于4周。相比之下，特异性抗体 由疫苗接种或感染引起的抗原经过数十年的抗原处理后，可以很容易地在人体血清中检测到 缺席（体液记忆）。这表明血清抗体水平在抗体分泌阶段受到调节 细胞及其特定前体（记忆 B 细胞）。对于两种细胞类型，寿命与连续性 更新被讨论为维持整个细胞群及其组成的手段，但这两个概念 既没有被物理证明也没有被证明。 在这个项目中，想要测量获得的抗体分泌细胞和记忆B细胞的DNA中的14C含量 来自 20 世纪 60 年代欧洲暴露于高浓度大气 14C 的捐助者。水平升高 从那时起，在静止的细胞中仍然可以检测到 14C 同位素，揭示它们的年龄。 14C分析需要 加速器质谱 (AMS) 确保对极低水平的 14C 进行精确定量 DNA 样本。与 Spalding 等人（Cell，第 122 卷，133 143，2005 年 7 月 15 日）类似，该分析将确定 抗体分泌细胞和记忆 B 细胞候选亚群的体内年龄并证明或反驳 这些细胞的寿命，支持或反对 B 细胞寿命作为体液记忆的关键要素。这 预期结果将为成功开发有效疫苗确定新的要求。