ALPHA BETA T CELL INDEPENDENT B CELL FUNCTION

ALPHA BETA T 细胞独立的 B 细胞功能

• 批准号: 2887089
• 负责人: ADRIAN Clive HAYDAY
• 金额: $ 23.6万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-15 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887089
• 关键词: B lymphocyte; T cell receptor; T lymphocyte; antibody formation; autoantibody; cell differentiation; gene mutation; gene rearrangement; immunoglobulin genes; laboratory mouse; polymerase chain reaction

DESCRIPTION (Adapted from Investigator's abstract): Mice congenitally lacking alpha/beta T-cells frequently display high levels of serum immunoglobulins (Igs). These Igs are of all isotypes which is surprising given the established dependence of IgG, and particularly IgE synthesis, on T-cells. Therefore, a novel pathway of B-cell maturation would appear to be active in alpha/beta T-cell deficient mice. This idea is supported by our finding that such mice also develop germinal centers, anatomical sites associated with T-cell-dependent B-cell maturation. The investigators, therefore, hypothesize that these mice display an heretofore uncharacterized capacity to T-B collaboration between B-cells and non alpha/beta T-cells. Notable among such cells are gamma/delta T-cells, that they have recently shown to "help" B-cells, by demonstrating that mice in which the only T-cells are gamma/delta T-cells, also display germinal centers. Gamma/delta T-cells have not heretofore been ascribed an effector function in B-cell maturation. To test their hypothesis, they plan to characterize B-cell biology in alpha/beta T-cell deficient mice. Interestingly, the antibodies formed in alpha/beta T-cell deficient mice are largely auto-reactive, targeting the same set of antigens as are targeted in human lupus patients. Other recently-derived data demonstrate that alpha/beta T-cell deficient mice indeed develop a lupus-like disease. The investigators, therefore, believe that characterization of the pathway can shed light on immuno-deficiency-associated autoimmune syndromes, such as have been reported in individuals with AIDS, and such as may be operative in one or more cohorts of lupus patients.

描述（改编自研究者摘要）：小鼠先天性 缺乏α/β T细胞经常显示高水平的血清 免疫球蛋白（Ig）。 这些免疫球蛋白是所有的同种型，这是令人惊讶的 考虑到IgG，特别是IgE的合成， T细胞 因此，一种新的B细胞成熟途径似乎是 在α/β T细胞缺陷小鼠中具有活性。 这一想法得到了我们的支持。 发现这些老鼠也会发育出生殖中心， 与T细胞依赖性B细胞成熟有关。 调查人员， 因此，假设这些小鼠表现出一种迄今为止尚未表征的 B细胞和非α/β T细胞之间的T-B协作能力。 这些细胞中值得注意的是γ/δ T细胞，它们最近 显示出“帮助”B细胞，通过证明小鼠，其中唯一的 T细胞是γ/δ T细胞，也显示出生殖中心。 伽玛/德尔塔 迄今为止，T细胞还没有被认为是B细胞中的效应子功能。 成熟 为了验证他们的假设，他们计划将B细胞 α/β T细胞缺陷小鼠的生物学。 有趣的是， 在α/β T细胞缺陷的小鼠中形成的大部分是自身反应性的， 靶向与在人类狼疮患者中靶向的相同的抗原组。 其他最近的数据表明，α/β T细胞缺乏 老鼠确实会患上类似狼疮的疾病。 因此，调查人员， 我相信，对这一途径的描述可以揭示 免疫缺陷相关的自身免疫综合征，如已被 在患有艾滋病的个体中报告，并且诸如可能在一个或多个患者中起作用， 更多的狼疮患者