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

人类浆细胞成熟

基本信息

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
项目类别：
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

项目摘要

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.

摘要：人类长寿浆细胞(LLPC)驻留在骨髓(BM)中，负责长期维持血清抗体水平。BM微粒子提供了重要因素，从根本上将早期产生的抗体分泌细胞(ASC)转化为CD138和BCMA成员的LLPC 肿瘤坏死因子受体超家族(TNFRSF)发挥着重要作用。在这个应用程序中，我们探索新旧骨髓微核中的CD138结合因子和长期建立和新发现的TNFRSF成员 LLPC的发展，以及如何调节抗体的高能功能分泌物决定LLPC的存活率。如果成功，这一应用程序将提供重要的基本机制用于耐久的疫苗设计。