Marginal zone B lymphocytes and blood borne pathogens

全面吸入性炭疽病发展的一个主要阶段是出现压倒性的菌血症。对血液传播的抗原提供保护的一种突出的细胞类型是边缘带B细胞。我们将尝试以聚谷氨酸胶囊和炭疽菌对边缘区B细胞的保护性抗原为靶点，在我们拟议的研究中，我们将使用突变小鼠来评估MZ B细胞在针对血源性抗原的保护性反应中的作用。我们将询问，聚谷氨酸胶囊是否可以通过尝试将其靶向于MZ B细胞，或者通过将其作为多价抗原保持构象来实现免疫原性。我们还将检查对PA的免疫反应是否可以 通过产生PA-C3d融合蛋白或使用PA-多糖偶联物试图将其重定向到MZ B细胞而增强。然后，我们将讨论一些抗原-C3d融合成功的原因是否因为抗原针对MZ B细胞，使用溶菌酶特异性B细胞和溶菌酶-C3d融合蛋白作为模型系统。我们将使用溶菌酶特异的MZ B细胞来尝试询问除了抗原本身之外，启动抗原特异的MZ B细胞的增殖需要什么。最后，我们将尝试确定抗原特异性的MZ B细胞，而不是毛囊B细胞，是否能够容易地捕获和呈递血液传播的抗原，从而激活原始T细胞。

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.