EARLY EVENTS IN MAMMALIAN B CELL DIFFERENTIATION

描述（改编自研究者摘要）：B中的关键事件 淋巴细胞形成，包括相关转录的表达 因子、受体复合物的组装和自身反应因子的消除 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， 来规范这一过程。 然而，关键球员 在这个规则中，很难确定，因为在许多情况下， 相同的因子被描述为淋巴细胞的激动剂或拮抗剂 一代 研究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淋巴细胞生成稳态调节。 B细胞前体严重 在怀孕或雌激素治疗的小鼠中， 缺乏免疫力的动物。 看来骨髓基质细胞 在雌激素的作用下产生淋巴细胞生成的抑制剂， 提出了表征和识别这种代理。 进一步的研究 提出鉴定可单独或共同起作用的其他调节剂 与激素一起影响B细胞的存活、扩增和分化 前体 还将开发允许这些延伸的测定法。 在小鼠系统中的研究与人类细胞的分析。 最后通过一个 将尝试设计新的文化体系，以支持增长 和分化的非常早期的祖群体下仔细 定义条件。 这些研究可能揭示激素水平如何 影响：1）移植后B细胞的再生，或 化疗; 2）B谱系肿瘤的生长;和3）化疗的过程。 自身免疫性疾病 因此，这些研究直接产生的信息 与妇女健康问题有关的研究，与年龄有关的研究， 激素疗法，免疫缺陷，自身免疫性疾病， 内分泌异常

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.