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呈递细胞（APC）在抗疟原虫的初次和二次免疫应答中的功能。我们假设，同种型转换的浆细胞将能够在整个初级和次级免疫反应对疟原虫抗原，这些细胞将用于调节在脾脏，特别是继发性感染后的生发中心的反应。我们已经提出了研究（目的1），以研究浆细胞表达约氏疟原虫感染后抗原呈递所必需的机制的能力，并确定这种细胞类型激活CD4[+] T细胞应答的能力，特别关注浆细胞的抗原呈递如何影响滤泡辅助T细胞的活性，一种参与抗体产生的特化T细胞。我们还将检查IgG[+]浆细胞和记忆B细胞在脾脏中的定位，以确定它们在脾脏中的定位如何影响次级应答的动力学（目的2）。浆细胞在疟原虫感染过程中呈递抗原的作用以前没有被考虑过，将这种细胞鉴定为功能性APC以及确定这种细胞类型如何调节二级抗体介导的免疫应答将进一步我们了解如何针对这种病原体产生长期免疫，这些信息将与成功的疫苗开发相关。

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.