EARLY EVENTS IN MAMMALIAN B CELL DIFFERENTIATION

哺乳动物 B 细胞分化的早期事件

• 批准号: 2703321
• 负责人: Paul Wayne Kincade
• 金额: $ 4.91万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2703321
• 关键词: EARLY; EVENTS; MAMMALIAN; CELL; DIFFERENTIATION

DESCRIPTION (Adapted from the Investigator's abstract): Key events in B lymphocyte formation, including the expression of relevant transcription factors, assembly of receptor complexes and elimination of autoreactive cells, are being defined at an increasing pace. Simultaneously, numerous molecules expressed in the bone marrow microenvironment with the potential to regulate this process have also been identified. However the key players in this regulation have been difficult to determine, since in many cases the same factors are described as either agonists or antagonists of lymphocyte generation. The investigator has completed studies recently that indicate that estrogen and other sex steroids can play an important role in the steady state regulation of B lymphopoiesis. B-cell precursors were severely depressed in pregnant or estrogen-treated mice, whereas they were elevated in hormone-deficient animals. It appears that bone marrow stromal cells produce an inhibitor of lymphopoiesis in response to estrogen and so studies are proposed to characterize and identify this agent. Further studies are proposed to identify other modulating agents that can act alone or together with hormones to affect survival, expansion and differentiation of B-cell precursors. Assays will also be developed that allow extension of these studies in the mouse system to analysis with human cells. Finally, an attempt will be made to devise new culture systems that support the growth and differentiation of very early progenitor populations under carefully defined conditions. These studies may reveal how hormone levels can influence: 1) the regeneration of B-cells following transplantation or chemotherapy; 2) the growth of B lineage tumors; and 3) the course of autoimmune diseases. Thus information generated in these studies directly relevant to women's health issues, age-related studies, the consequences of hormone therapy, to immunodeficiencies, to autoimmune diseases and to endocrine abnormalities.

描述(改编自调查者摘要)：B中的关键事件 淋巴细胞形成，包括相关转录的表达 因子、受体复合体的组装和自身反应的消除 细胞，正在以越来越快的速度被定义。同时，众多 在骨髓微环境中表达的分子具有潜在的 对这一过程的监管也已确定。然而，关键的参与者 在这一规定中一直很难确定，因为在许多情况下 同样的因子被描述为淋巴细胞的激动剂或拮抗剂。 一代。调查人员最近完成的研究表明， 雌激素和其他性类固醇可以在 B淋巴细胞生成的稳态调节。B细胞前体细胞严重 在怀孕或雌激素治疗的小鼠中，它们被抑制，而它们被升高 在荷尔蒙缺乏的动物身上。看来，骨髓基质细胞 产生一种对雌激素反应的淋巴生成抑制物，因此研究 被提议用来表征和鉴定这种病原体。进一步的研究是 建议确定其他可以单独或共同作用的调节剂 激素对B细胞存活、扩增和分化的影响 先驱物。还将开发允许扩展这些技术的检测方法 在小鼠系统中进行研究，以分析与人类细胞。最后，一个 将尝试设计新的文化系统来支持增长 和分化的非常早期的祖先群体在仔细 已定义的条件。这些研究可能揭示荷尔蒙水平如何 影响：1)移植后B细胞的再生或 化疗；2)B系肿瘤的生长；3)病程 自身免疫性疾病。因此，在这些研究中产生的信息直接 与妇女健康问题有关，与年龄有关的研究， 激素治疗，免疫缺陷，自身免疫性疾病和 内分泌异常。