B CELL ACTIVATION IN AUTOIMMUNITY & LYMPHOPROLIFERATION

自身免疫中的 B 细胞激活

• 批准号: 3156656
• 负责人: Argyrios N Theofilopoulos
• 金额: $ 13.72万
• 依托单位: SCRIPPS CLINIC AND RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-06-01 至 1989-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3156656
• 关键词: B lymphocyte; T lymphocyte; autoimmune disorder; cell differentiation; immunoglobulins; leukocyte activation /transformation; lymphokines; orphan disease /drug; systemic lupus erythematosus

A variety of immunologic, virologic, hormonal, and genetic abnormalities have been catalogued in murine strains with with systemic lupus erythematosus (SLE)-like syndromes. However, no common link or molecular basis for such abnormalities has yet been identified. Among the various abnormalities, B cell hyperactivity leading to autoantibody production is the common and cardinal feature of all SLE murine strains, as well as of humans with SLE. Whether this B cell abnormality is primary or secondary to helper or suppresor T cell defects remains controversial and and unclear at the present. A large body of recent work indicates that proliferative and differentiative events in B and T cell development are induced by a cascade of antigen-specific and nonspecific soluble mediators elaborated by activated T cells, macrophages, and perhaps other elements of the immune systems. In order to clarify further the essential immunologic abnormalities that lead to autoimmune disorders and perhaps devise means for their molecular analysis, we propose to: (a) measure the effects of soluble T cell-derived factors with known activities on B cells of SLE and normal control murine strains; (b) assess the in vitro elaboration of soluble mediators by limphoid cells of SLE and control strains that might influence B cell differentiative and muturational processes and, if identified, determine their levels, cellular origin, mode of action, and relationship to the disease state: (c) isolate and biochemically characterize the factos, attempt to produce antibodies against them and subsequently assess the in vitro and in vivo effects of the factors and of respective antibodies; and (d) develop new lines of SLE mice defective in expression of acceptor sites for T cell-derived signals so as to ascertain the in vivo importance of the factors and of the target cell component in disease expression. These studies will clarify the means of B cell activation in systemic autoimmune diseases, provide further understanding of the interplay among lymphokines that participate in cellular and humoral immune responses, and may allow, in the future, molecular analysis and modification of this and related disorders.

各种免疫学、病毒学、激素和遗传异常 已经在系统性红斑狼疮的小鼠品系中被分类 红斑狼疮样综合征。 然而，没有共同的链接或分子 这种不正常现象的依据尚未查明。 的各种 异常，B细胞过度活跃导致自身抗体产生， 所有SLE鼠株的共同和主要特征，以及 SLE患者。 这种B细胞异常是原发性还是继发性的 辅助或抑制T细胞缺陷仍然存在争议， 在目前。 大量的近期研究表明， B和T细胞发育中的分化事件由级联反应诱导 抗原特异性和非特异性可溶性介质， 活化的T细胞，巨噬细胞，也许还有免疫系统的其他成分， 系统. 为了进一步阐明免疫学的基本原理， 导致自身免疫性疾病的异常， 对于它们的分子分析，我们建议：（a）测量 对SLE的B细胞具有已知活性的可溶性T细胞衍生因子， 正常对照鼠品系;（B）评估体外加工 可溶性介质的系统性红斑狼疮和对照菌株， 影响B细胞分化和突变过程， 确定其水平、细胞来源、作用方式，以及 与疾病状态的关系：（c）分离和生物化学 描述这些事实，试图产生抗体， 随后评估这些因子的体外和体内效应， 各自的抗体;和（d）开发新的SLE小鼠品系，其在以下方面有缺陷： T细胞来源的信号的受体位点的表达，以便确定 这些因子和靶细胞成分在体内的重要性， 疾病表达。 这些研究将阐明B细胞的意义 激活系统性自身免疫性疾病，提供进一步的了解 参与细胞和体液免疫的淋巴因子之间的相互作用 免疫反应，并可能允许，在未来，分子分析和 改变这种疾病和相关疾病。