B CELLS IN MURINE SLE

建议研究B细胞在自发性 近交系小鼠利用同源品系产生系统性自身免疫 其在LPR基因座上是纯合的。 这些动物发展成弥漫性的 淋巴结病和多种自身抗体。 广泛的前期工作 在这些老鼠身上发现了明显的T细胞异常 他们的B细胞 没有被仔细研究过：特别是，LPR的作用 B细胞中的Ly-1基因和Ly-1+ B细胞亚群的作用尚不清楚。 本提案将解决B细胞在lpr诱导的细胞凋亡中的功能。 自身免疫有三种具体的方式：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 将探讨自身抗体所需的T-B协作的性质， 在LPR小鼠中形成。 3)它将决定Ly-1+ B细胞在 在LPR小鼠中自身抗体的产生。 在这三个领域的实验将 依赖于双嵌合体小鼠的产生，其中供体来源于 淋巴细胞的免疫球蛋白同种异型或表面 表型标记 因此可以确定正常B 可以在LPR环境中驱使细胞产生自身抗体; lpr小鼠自身抗体产生的协同作用是否是H-2 Ly-1+和常规B细胞的相对作用是什么？ 亚群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分选。 这些研究将进一步提供 了解B细胞如何被诱导形成自身抗体， 重要的SLE小鼠模型，并应有助于关注未来的研究 这种疾病的免疫调节异常

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.