B CELLS IN MURINE SLE

小鼠 SLE 中的 B 细胞

• 批准号: 2080169
• 负责人: ROBERT A. EISENBERG
• 金额: $ 15.47万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-30 至 1995-04-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2080169
• 关键词: B lymphocyte; T lymphocyte; antibody formation; autoantibody; autoimmunity; cell cell interaction; disease /disorder model; enzyme linked immunosorbent assay; flow cytometry; gene expression; genetic strain; laboratory mouse; systemic lupus erythematosus; tissue mosaicism

It is proposed to investigate the role of the B cell in spontaneous systemic autoimmunity in inbred mice by utilizing congenic mouse strains which are homozygous at the lpr locus. These animals develop diffuse lymphadenopathy and a variety of autoantibodies. Extensive previous work has documented marked T-cell abnormalities in these mice. Their B cells have been less carefully investigated: specifically, the role of the lpr gene in the B cells and the role of the Ly-1+ B-cell subset are unknown. The present proposal will address the function of the B cell in lpr-induced autoimmunity in three specific ways: 1) It will determine the role of lpr gene expression in B cells for autoantibody formation in lpr mice. 2) It will explore the nature of T-B collaboration required for autoantibody formation in lpr mice. 3) It will determine the role of Ly-1+ B cells in autoantibody production in lpr mice. Experiments in all three areas will rely on the generation of double-chimaeric mice in which the donor origin of lymphocytes will be determined by immunoglobulin allotype or surface phenotype markers. It will thus be possible to establish whether normal B cells can be driven into autoantibody production in an lpr environment; whether collaboration for autoantibody production in lpr mice is H-2 restricted; and what relative roles the Ly-1+ and conventional B-cell subsets play in this disease. The latter issue will also be addressed by sorting of autoantibody-forming cells. These studies will provide further understanding of how B cells are induced to form autoantibodies in an important murine model of SLE and should help to focus future research toward the essential immunoregulatory abnormalities in this disease.

建议研究B细胞在自发的作用 通过利用过热小鼠菌株，在近交小鼠中的系统性自身免疫性 LPR基因座是纯合的。 这些动物发展弥漫 淋巴结肿大和各种自身抗体。 大量以前的工作 已经记录了这些小鼠的明显T细胞异常。 他们的B细胞 不太仔细研究：具体来说，LPR的作用 B细胞中的基因和LY-1+ B细胞子集的作用尚不清楚。 本提案将解决LPR诱导的B单元的功能 以三种特定方式自动免疫：1）它将决定LPR的作用 LPR小鼠中自身抗体形成的B细胞中的基因表达。 2）它 将探讨自动抗体所需的T-B协作的性质 LPR小鼠的形成。 3）它将确定LY-1+ B细胞在 LPR小鼠的自身抗体产生。 在所有三个领域的实验将 依靠捐赠者起源的双核小鼠的产生 淋巴细胞将由免疫球蛋白同种型或表面确定 表型标记。 因此，可以确定是否正常b 在LPR环境中，可以将细胞驱动到自身抗体的产生中； LPR小鼠中自身抗体生产的协作是否为H-2 受限制的;以及LY-1+和常规B细胞的相对作用 子集在这种疾病中发挥作用。 后一个问题也将由 自身抗体形成细胞的排序。 这些研究将进一步提供 了解如何诱导B细胞在A中形成自身抗体 SLE的重要鼠模型，应有助于集中未来的研究 迈向这种疾病的基本免疫调节异常。