Long-lived antibody secreting cells

描述(由申请人提供)：长寿抗体分泌细胞(ASCs)或浆细胞形成的潜在因素尚不清楚。此R21应用的主要目的是确定在对T细胞依赖(TD)和T细胞非依赖(TI)抗原的体液免疫反应的早期阶段形成的ASCs是否长期存活。拟议的实验将遵循初步数据，这些数据表明TD和TI抗原都能诱导形成长寿命的ASCs。其他实验将测试针对T细胞非依赖抗原而形成的ASCs是否需要迁移到骨髓中才能长期存活。我们将结合正常的和基因操作的小鼠品系来解决这些问题。具体地说，我们将：1)定义由主要的TI和TD抗原产生的早期ASCs的寿命，以及2)定义保留在脾中的TI-1抗原诱导的ASCs的寿命。 与公共卫生相关：产生分泌浆细胞的长寿命抗体的潜在因素尚不清楚。我们的研究将挑战当前的教条，即T细胞非依赖性抗原无法诱导长寿浆细胞的形成。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意义。

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.