Project 3 - A Role for Plasma Cells as Antigen Presenting Cells During Malaria

原生动物寄生虫疟原虫是疟疾的致病菌，疟疾仍然是当今世界最突出的公共卫生挑战之一。这个项目的总体目标是研究浆细胞作为抗原提呈细胞(APC)在针对疟原虫的初级和二级免疫反应中的功能。我们假设同种类型转换的浆细胞将能够在针对疟原虫的初级和次级免疫反应中呈递抗原，并且这些细胞将有助于调节脾中的生发中心反应，特别是在二次感染之后。我们已经提出研究(目标1)调查感染约氏疟原虫后浆细胞表达抗原提呈所需机制的能力，并确定这种细胞类型激活CD4[+]T细胞反应的能力，特别是确定浆细胞的抗原提呈如何影响滤泡辅助T细胞的活性，滤泡辅助T细胞是参与抗体产生的一种特殊的T细胞亚群。我们还将检查免疫球蛋白G[+]浆细胞和记忆B细胞在脾中的定位，以确定它们在脾中的定位如何影响二次反应的动力学(AIMS 2)。浆细胞在疟原虫感染过程中呈递抗原的作用以前还没有被考虑过，确定这个细胞是一个功能性的APC以及确定这种细胞类型如何调节二次抗体介导的免疫反应将进一步加深我们对这种病原体的长期免疫是如何产生的理解，这将是与成功的疫苗开发相关的信息。

The protozoan parasite Plasmodium is the causitive agent of malaria, which remains one of the most prominent public health challenges in the world today. The overall goal of this project is to examine the function of plasma cells as antigen presenting cells (APCs) during a primary and secondary immune response against Plasmodium. We hypothesize that isotype-switched plasma cells will be able to present antigen throughout the primary and secondary immune response against Plasmodium and that these cells will serve to regulate the germinal center response in the spleen, particularly following a secondary infection. We have proposed studies (Aims 1) to investigate the ability of plasma cells to express the machinery necessary for antigen presentation following infection with P. yoelii and to determine the capacity of this cell type to activate a CD4[+] T-cell response, with a specific focus on determining how antigen presentation by plasma cells influences the activity of follicular helper T cells, a specialized subset of T cells involved in antibody production. We will also examine the localization of IgG[+] plasma cells and memory B cells in the spleen to determine how their positioning in the spleen influences the kinetics of a secondary response (Aims 2). A role for plasma cells in the presentation of antigen during Plasmodium infection has not been considered previously, and identifying this cell as a functional APC as well as determining how this cell type regulates a secondary antibody-mediated immune response will further our understanding of how long-term immunity is generated against this pathogen, information that will be pertinant for successful vaccine development.