Immunobiology of B Cell Differentiation

B 细胞分化的免疫生物学

• 批准号: 8389662
• 负责人: KENNETH Allan DORSHKIND
• 金额: $ 34.61万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8389662
• 关键词: Address; Adult; Autoimmunity; B cell differentiation; B-Cell Development; B-Lymphocytes; Blood Circulation; Bone Marrow; CD19 gene; Cell Lineage; Cells; Cytokine Receptors; Data; Dependency; Development; Embryo; Embryonic Development; Estrogens; Exhibits; Fetal Liver; Fetus; Gene Expression Profile; Goals; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Immunobiology; Immunologic Deficiency Syndromes; Interleukin-7; Laboratories; Lymphopoiesis; Maintenance; Mouse Strains; Mus; Organ; Phenotype; Population; Process; Production; Public Health; Regulation; Resolution; Signal Transduction; Site; Specific qualifier value; Staging; Stem cells; Stimulus; TSLP gene; Testing; Tissues; Transcriptional Regulation; Wnt proteins; Yolk Sac; abstracting; base; cytokine; embryo tissue; fetal; gain of function; leukemogenesis; progenitor; programs; research study; residence; response; transcription factor

Project Description/Abstract Numerous studies have revealed differences in the transcriptional regulation of B lymphopoiesis in the embryo and the adult. In addition, B lineage cells isolated from fetal liver and adult bone marrow exhibit differential sensitivity to selected cytokines. The central hypothesis of this proposal is that these differences exist because B-1 progenitors and their progeny are the dominant B lineage cells present in the embryo and that the intra- and extra-cellular signals to which they respond are distinct from those that regulate the development of B-2 B cells. This premise is based on recent studies from our laboratory demonstrating that B-1 B cell progenitors, identified by their unusual Lin- CD45Rlow/- CD19+ phenotype, are the major B cell progenitor population present in the fetus. The goals of this proposal are to determine when and where in the embryo B-1 progenitors emerge and test the hypothesis that the regulatory controls operative on them are distinct from those in the B-2 lineage. Aim 1 will take advantage of recent advancements in the phenotypic resolution of B-1 and B-2 progenitors to define when and in which embryonic tissues B-1 and B-2 B specified progenitors appear and expand and test the hypothesis that B-1 B cells are part of the primitive wave of hematopoiesis. Experiments in Aim 2 will use loss and gain of function approaches in order to identify transcription factors whose expression is required for B-1 development and test the hypothesis that the transcriptional regulation of B-1 and B-2 development is distinct. Fetal and adult B lineage cells exhibit distinct responses to various microenvironmental and systemic signals, and we propose that these differences are due to the differential effects of these stimuli on B-1 and B-2 progenitors. Testing this possibility is the goal of Aim 3. Taken together, the results form this study will provide a comprehensive picture of fetal B cell development that is of relevance to the fields of immunodeficiency, leukemogenesis, and hematopoietic stem cell transplantation.

项目描述/摘要 大量研究揭示了B淋巴管的转录调节的差异 在胚胎和成人中。此外，从胎儿肝脏和成人骨骼分离的B谱系细胞 骨髓对选定的细胞因子具有差异敏感性。中心假设 提议是存在这些差异，因为B-1祖细胞及其后代是 存在于胚胎中的主要B谱系细胞，并且细胞内和细胞外信号至 他们的反应与调节B-2 B细胞发展的那些不同。这 前提是基于我们实验室的最新研究，证明B-1 B细胞 祖细胞，通过其不寻常的lin- cd45rlow/-cd19+表型，是主要的B细胞 胎儿中存在的祖细胞种群。该建议的目标是确定何时和 在胚胎中，B-1祖细胞出现并检验了调节控制的假设 它们上的手术与B-2谱系中的操作不同。 AIM 1将利用最近的优势 B-1和B-2祖细胞的表型分辨率的进步定义何时和中 哪些胚胎组织B-1和B-2 B指定的祖细胞出现并扩展和测试 假设B-1 B细胞是造血作品的原始波的一部分。 AIM中的实验 2将使用功能方法的损失和增益，以识别转录因子 B-1开发需要表达并检验转录的假设 B-1和B-2发育的调节是不同的。胎儿和成人B谱系细胞表现出不同的 对各种微环境和全身信号的响应，我们建议这些 差异是由于这些刺激对B-1和B-2祖细胞的差异作用。测试 这种可能性是目标3的目标。总之，结果表格将提供一个 胎儿B细胞发育的全面图片与领域有关 免疫缺陷，白血病和造血干细胞移植。