Human Plasma Cell Maturation & Maintenance through CD138, TNFRSF, and Modulation of Ig Secretion

人类浆细胞成熟

• 批准号: 10660723
• 负责人: Frances Eun-Hyung Lee
• 金额: $ 78.6万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-21 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660723
• 关键词: Adult; Affect; Antibodies; Antigens; Atlases; Binding; Biological Assay; Biology; Blood; Bone Marrow; Cell Maintenance; Cell Maturation; Cell Survival; Cells; Cellular Morphology; Chronology; Development; Epigenetic Process; Excision; Generations; Genetic Transcription; Genus Mentha; Glycolysis; Growth Factor; Heterogeneity; Human; Human Resources; Immunity; Immunoglobulin-Secreting Cells; Immunoglobulins; In Vitro; Lightning; Link; MCL1 gene; Maintenance; Malignant Neoplasms; Molecular; OX40; Pathogenicity; Phenotype; Plasma Cells; Plasmablast; Play; Proliferating; Property; Proteomics; Recovery; Role; SNAP receptor; Serum; Signal Pathway; Signal Transduction; Stress; Surface; T-Cell Activation; TNF gene; TNFRSF17 gene; Testing; Time; Tumor Necrosis Factor Receptor; Vaccination; Vaccine Design; Vaccines; angiogenesis; autocrine; cell transformation; cellular resilience; cytokine; heparin proteoglycan; herpesvirus entry mediator; high voltage electron microscopy; in vitro testing; inhibiting antibody; inhibitor; lymph nodes; member; midkine; migration; novel; plasma cell development; prevent; programs; promote resilience; receptor; resilience; secretory protein; single cell analysis; single-cell RNA sequencing; transcriptome; vaccine response

Abstract: Human long-lived plasma cells (LLPC) reside in the bone marrow (BM) and are responsible for the long-term maintenance of serum antibody levels. The BM microniche provides important factors to fundamentally transform early-minted antibody secreting cells (ASC) into LLPC for which CD138 and BCMA - a member of the TNF receptor superfamily (TNFRSF) - play an important role. In this application, we explore old and new CD138 binding factors in the BM microniche and long-established and newly discovered TNFRSF members in the development of LLPC, as well as understanding how modulating the high energy function of antibody secretion determines LLPC survival. If successful, this application will provide the basic mechanisms important for durable vaccine design.

抽象的： 人类长寿命的浆细胞（LLPC）位于骨髓（BM）中，并负责长期 维持血清抗体水平。 BM Microniche提供了重要的因素 将早期染色抗体分泌细胞（ASC）转化为CD138和BCMA的LLPC- TNF受体超家族（TNFRSF） - 发挥重要作用。在此应用程序中，我们探索新旧 CD138 BM微米和长期建立和新发现的TNFRSF成员的CD138结合因子 LLPC的发展，以及了解如何调节抗体的高能量功能 分泌决定了LLPC生存。如果成功，此应用将提供重要的基本机制 用于耐用的疫苗设计。