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病原体，疟疾仍然是当今世界上最突出的公共卫生挑战之一。本项目的总体目标是研究浆细胞作为抗原提呈细胞（APCs）在对疟原虫的初级和次级免疫反应中的功能。我们假设，同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，并且这些细胞将调节脾脏的生发中心反应，特别是在继发性感染后。我们提出了一些研究（目的1）来研究约氏疟原虫感染后浆细胞表达抗原呈递所需机制的能力，并确定这种细胞类型激活CD4[+] T细胞反应的能力，特别关注于确定浆细胞抗原呈递如何影响滤泡辅助性T细胞的活性，滤泡辅助性T细胞是参与抗体产生的T细胞的一个特殊亚群。我们还将研究脾脏中IgG[+]浆细胞和记忆B细胞的定位，以确定它们在脾脏中的定位如何影响二次反应的动力学（目的2）。在疟原虫感染期间，浆细胞在抗原呈递中的作用以前没有被考虑过，将这种细胞确定为功能性APC以及确定这种细胞类型如何调节二级抗体介导的免疫反应，将进一步了解如何产生针对这种病原体的长期免疫，这些信息将与成功开发疫苗有关。

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.