Long-lived antibody secreting cells

描述（由申请方提供）：长寿抗体分泌细胞（ASC）或浆细胞形成的潜在因素尚不清楚。这项R21申请的主要目的是确定在对T细胞依赖性（TD）和T细胞非依赖性（TI）抗原的体液免疫应答的最早阶段形成的ASC是否是长寿的。所提出的实验将遵循初步数据，表明TD和TI抗原都引起长寿命ASC的形成。另外的实验将测试响应于T细胞非依赖性抗原而形成的ASC是否需要迁移到骨髓中以变得长寿。我们将使用正常和基因操作的小鼠品系的组合来解决这些问题。具体而言，我们将：1）确定通过原代TI和TD抗原产生的早期ASC的寿命，和2）确定保留在脾脏中的TI-1抗原诱导的ASC的寿命。 公共卫生相关性：尚不清楚产生长寿命抗体分泌浆细胞的潜在因素。我们的研究将挑战目前的教条，即T细胞非依赖性抗原不能诱导长寿命浆细胞的形成。这些研究对对抗抗体介导的自身免疫性疾病的治疗策略具有直接影响。

DESCRIPTION (provided by applicant): The factors underlying the formation of long-lived antibody secreting cells (ASCs) or plasma cells are unknown. The main objective of this R21 application is to establish whether ASCs that form during the earliest phases of the humoral immune response to T cell dependent (TD) and T cell independent (TI) antigens are long-lived. The proposed experiments will follow from preliminary data suggesting that both TD and TI antigens elicit the formation of long-lived ASCs. Additional experiments will test whether ASCs that form in response to T cell independent antigen require migration into the bone marrow to become long-lived. We will address these questions using a combination of normal and genetically manipulated mouse lines. Specifically we will: 1) Define the lifespan of early ASCs produced via primary TI and TD antigens, and 2) Define the lifespan of TI-1 antigen-induced ASCs retained in the spleen. PUBLIC HEALTH RELEVANCE: The factors underlying the generation of long-lived antibody secreting plasma cells are not understood. Our studies will challenge current dogma that T cell independent antigens fail to induce the formation of long-lived plasma cells. These studies have direct implications for therapeutic strategies to combat antibody-mediated autoimmune diseases.