Marginal zone B lymphocytes and blood borne pathogens

边缘区 B 淋巴细胞和血源性病原体

• 批准号: 6602388
• 负责人: SHIV Subramaniam PILLAI
• 金额: $ 28.96万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6602388
• 关键词: B lymphocyte; Bacillus anthracis; Bacillus subtilis; T lymphocyte; anthrax; antibody specificity; antigen presentation; bacteria infection mechanism; bacterial antigens; bactericidal immunity; bioterrorism /chemical warfare; chimeric proteins; enzyme linked immunosorbent assay; gene targeting; genetically modified animals; hemotoxin; host organism interaction; humoral immunity; laboratory mouse; lysozyme; polyglutamates; polymerase chain reaction; pulmonary respiration; virulence

A major stage in the development of full-blown inhalation anthrax is the development of overwhelming bacteremia. A prominent cell type that provides protection against blood borne antigens is the marginal zone B cell. Attempts will be made to target the polyglutamate capsule and the protective antigen of anthrax to marginal zone B cells, in our proposed studies we will use mutant mice in an attempt to evaluate the role of MZ B cells in protective responses against blood-borne antigens. We will ask whether the polyglutamate capsule can be rendered immunogenic either by attempting to target it to MZ B cells, or by preserving it conformationally as a multivalent antigen. We will also examine whether the immune response to PA can be enhanced by generating a PA-C3d fusion protein or by using a PA-polysaccharide conjugate in an attempt to redirect it to MZ B cells. We will then address the general issue as to whether the reason why some antigen-C3d fusions have been successful is because the antigen was targeted to MZ B cells, using lysozyme specific B cells and lysozyme-C3d fusion proteins as a model system. We will use lysozyme-specific MZ B cells to attempt to ask what is required beyond antigen per se to initiate proliferation of antigen-specific MZ B cells. Finally we will attempt to determine whether antigen-specific MZ B cells, as opposed to follicuar B cells, can readily capture and present blood borne antigens, and thus activate na'fve T cells.

一个主要阶段的发展，全面吸入炭疽是压倒性菌血症的发展。边缘区B细胞是一种主要的抗血源性抗原的细胞类型。将尝试将聚谷氨酸囊和炭疽保护性抗原靶向边缘区B细胞，在我们提出的研究中，我们将使用突变小鼠，试图评估MZ B细胞在对抗血源性抗原的保护性应答中的作用。我们将询问是否可以通过尝试将聚谷氨酸胶囊靶向MZ B细胞或通过将其构象保留为多价抗原来使其具有免疫原性。我们还将研究是否可以免疫反应PA 通过产生PA-C3 d融合蛋白或通过使用PA-多糖缀合物以试图将其重定向至MZ B细胞来增强。然后，我们将使用溶菌酶特异性B细胞和溶菌酶-C3 d融合蛋白作为模型系统，解决一些抗原-C3 d融合成功的原因是否是因为抗原靶向MZ B细胞的一般问题。我们将使用溶菌酶特异性MZ B细胞，试图了解除了抗原本身之外，还需要什么来启动抗原特异性MZ B细胞的增殖。最后，我们将试图确定抗原特异性MZ B细胞，而不是滤泡B细胞，是否可以容易地捕获和呈递血源性抗原，从而激活幼稚T细胞。