Plasma Cell Priming

项目摘要 自身反应性抗体产生的细胞和分子事件 自身免疫性仍然知之甚少。值得注意的是，边缘区（MZ）B细胞是 富含自身反应性B细胞，并且已知产生抗体分泌血浆 与其他B细胞相比，这个R21项目的中心是 了解MZ B细胞产生血浆的分子机制 细胞与加速动力学，重点是定义细胞外的线索和相关的 引发MZ B细胞分化的细胞内信号传导途径。中央 指导这项工作的假设是mTOR/mTORC 1激酶，一种新兴的生物标志物， 在狼疮和相关的自身免疫性疾病中，BAFF受体信号传导和 相关浆细胞基因的表达以促进抗体的快速诱导 合成.为了验证这一假设，我们将：1）定义mTOR/mTORC 1信号传导的作用 在浆细胞引发中，以及2）探索驱动血浆的细胞外输入的身份 原位细胞引发。这些研究将增进对这些现象背后的过程的了解。 所有浆细胞的产生，包括那些分泌致病性自身反应的浆细胞， 抗体的

Project summary The cellular and molecular events underlying the generation of self-reactive antibodies in autoimmunity remain poorly understood. Notably, marginal zone (MZ) B cells are enriched for self-reactive B cells, and are known to generate antibody-secreting plasma cells exceptionally quickly compared to other B cells. This R21 project centers on understanding the molecular mechanisms through which MZ B cells generate plasma cells with accelerated kinetics, with a focus on defining extracellular cues and associated intracellular signaling pathways that prime MZ B cells for differentiation. The central hypothesis guiding this work is that the mTOR/mTORC1 kinase, an emerging biomarker in lupus and related autoimmune diseases, couples BAFF-receptor signaling and expression of relevant plasma cell genes to facilitate rapid induction of antibody synthesis. To test this hypothesis we will: 1) Define the role of mTOR/mTORC1 signaling in plasma cell priming, and 2) Explore the identity of extracellular inputs driving plasma cell priming in situ. These studies will enhance knowledge of the processes underlying the generation of all plasma cells including those secreting pathogenic self-reactive antibodies.