Long-lived CD19-positive plasma cells

描述（由申请方提供）：维持针对外源和自身抗原的血清抗体所需的信号和事件仍不明确。本申请的主要目的是评估骨髓（BM）中最近形成的分泌抗体的浆细胞在这些过程中的作用，并定义最近形成的和长寿命的浆细胞用于避免细胞死亡的细胞因子。为了实现这些目标，我们将：1）定义新形成的BM PC在长寿命抗体介导的免疫中的作用; 2）定义新形成的和长寿命的BM PC在抗体介导的自身免疫中的作用;和3）定义IL-5和BAFF家族细胞因子在维持TI抗原诱导的PC中的作用。这些研究将增强对非自身和自身抗原的长寿命抗体应答的形成和维持的潜在过程的认识，从而为优化疫苗接种策略和对抗抗体介导的自身免疫性疾病提供信息。 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。这些研究将定义持久抗原在长寿命抗体介导的免疫中的作用，同时也挑战了目前的教条，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或相反诱导长寿免疫的治疗策略具有直接影响。

DESCRIPTION (provided by applicant): The signals and events required for maintaining serum antibodies to foreign and self- antigens remain poorly defined. The main goals of this application are to evaluate the role of recently formed antibody secreting plasma cells in the bone marrow (BM) in these processes, and to define the cytokines that recently formed and long-lived plasma cells employ to avoid cell death. To achieve these objectives we will: 1) Define the role of newly formed BM PCs in long-lived antibody-mediated immunity; 2) Define the role of newly formed and long-lived BM PCs in antibody-mediated autoimmunity; and 3) Define the roles of IL-5 and BAFF family cytokines in the maintenance of TI antigen-induced PCs. These studies will enhance knowledge of the processes underlying formation and maintenance of long-lived antibody responses to both non-self and self-antigens, and consequently inform strategies to optimize vaccination strategies and combat antibody mediated autoimmune disease. PUBLIC HEALTH RELEVANCE: The factors underlying the generation of long-lived antibody secreting plasma cells are not understood. These studies will define the role of persisting antigen in long-lived antibody-mediated immunity, while also challenging the 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 or conversely to induce long-lived immunity.