Understanding the mechanisms of immune receptor signalling and how to target this process in disease

了解免疫受体信号传导机制以及如何针对疾病中的这一过程

• 批准号: 2897399
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2897399
• 关键词: Understanding; mechanisms; immune; receptor; signalling

B lymphocytes play a crucial role in adaptive immunity, being responsible for antibody production as well as contributing to antigen presentation and cytokine secretion to coordinate the immune response. Stimulation of B cells occurs primarily through the B-cell receptor (BCR), a surface-exposed membrane-integrated immunoglobulin. Antigen binding to the BCR stimulates a number of downstream signalling pathways that control B-cell differentiation, proliferation and migration. Dysregulation of BCR signalling is responsible for human malignancies such as lymphoid leukaemia and lymphoma and is also associated with various immunological disorders. Because of its crucial importance in B cell physiology, the BCR has been intensively investigated for many years. In our recent work, we have uncovered a novel mechanism controlling BCR clustering and signalling, which involves the inositol phosphatase INPP5B. Preliminary results also suggest INPP5B is important for B cell physiology and the proliferation of lymphoma cells. The goal of this project is to build upon our work to date to decipher the molecular details of how INPP5B controls BCR dynamics, how this occurs in time and space, and to determine its significance for normal B cell functions as well as those occurring in cancerous B cells. The project will involve cell biology and immunological techniques, which will include proteomics, high-end live and fixed cell imaging, combined with immune phenotyping, cancer cell proliferation and migration assays. The findings will provide major new insights into the BCR and will have significant implications for our understanding of the healthy immune system, as well as B cell disorders such as leukaemia and lymphoma.

B 淋巴细胞在适应性免疫中发挥着至关重要的作用，负责抗体的产生以及抗原呈递和细胞因子分泌以协调免疫反应。 B 细胞的刺激主要通过 B 细胞受体 (BCR) 发生，BCR 是一种表面暴露的膜整合免疫球蛋白。抗原与 BCR 结合会刺激许多控制 B 细胞分化、增殖和迁移的下游信号通路。 BCR 信号传导失调是导致淋巴白血病和淋巴瘤等人类恶性肿瘤的原因，并且还与各种免疫性疾病有关。由于 BCR 在 B 细胞生理学中至关重要，多年来人们对 BCR 进行了深入研究。在我们最近的工作中，我们发现了一种控制 BCR 聚类和信号传导的新机制，其中涉及肌醇磷酸酶 INPP5B。初步结果还表明 INPP5B 对于 B 细胞生理学和淋​​巴瘤细胞的增殖很重要。该项目的目标是在我们迄今为止的工作基础上破译 INPP5B 如何控制 BCR 动态的分子细节、其在时间和空间上如何发生，并确定其对正常 B 细胞功能以及癌性 B 细胞功能的重要性。 B细胞。该项目将涉及细胞生物学和免疫学技术，其中包括蛋白质组学、高端活细胞和固定细胞成像，以及免疫表型分析、癌细胞增殖和迁移测定。这些发现将为 BCR 提供重要的新见解，并将对我们了解健康免疫系统以及白血病和淋巴瘤等 B 细胞疾病产生重大影响。