Anti-Sm B-1 Cell Differentiation and Function

描述：(申请人提供)：本项目的远景目标是 了解B细胞耐受性，以及耐受性在疾病中是如何被打破的。焦点 是B细胞上对Smith(Sm)抗原的特异性，Smith(Sm)是一种核糖核蛋白 在所有细胞中发现的RNA剪接，以及免疫系统中的一个靶点 系统性红斑狼疮。了解抗Sm B细胞的调节作用 利用抗Sm B重排的Ig H链转基因(2-12H TG)小鼠 已生成单元格。脾组织中存在抗Sm B细胞。 非自身免疫性2-12h TG小鼠，多数为过渡性B细胞。此外, 在这些小鼠中，大约30%的腹膜B-L细胞是抗Sm的。虽然 这些小鼠对Sm免疫有反应，表明保持了耐受性 由于疏忽，免疫前血清中的抗Sm水平与 非甘油三酯小鼠。这是矛盾的，因为B-L细胞负责大部分 循环中的IgM。在自身免疫的MRL/LPR小鼠中，抗Sm B细胞被激活，但 他们不区分为B-L。这个应用程序的三个目标测试 假设：抗Sm移行B细胞受抗原驱动 分化为B-1，但它们被表达抑制激活 CD5是B细胞活化的负性调节因子。在自身免疫的小鼠中， B-1分化受阻，抗Sm B细胞分化为B-2，其中 它们更容易被激活。第一个目标是，抗Sm的能力 要分化为B-1的过渡性B细胞将通过转移 2~12HTg过渡期。B细胞对非甘油三酯小鼠。此外，V曲目 将分析212H TG小鼠的抗Sm移行细胞和B-1细胞 确定对B-L的分化是否具有选择性。在第二个目标中， 抗Sm B-1细胞的功能将在体外和体内进行评估，并发挥作用 在2-12h的TG/CD54-/-小鼠中检测到CD5的表达。在最终目标中，B的命运 正常分化为B-L的细胞将在自身免疫中被确定 Mrl/lpr小鼠采用B-L分化的TG模型系统。

DESCRIPTION: (provided by applicant): The long-range goal of this project is to understand B cell tolerance and how tolerance is broken in disease. The focus is on B cells specific for the Smith (Sm) antigen, a ribonucleoprotein involved in RNA splicing found in all cells, and a target of the immune system in systemic lupus erythematosus. To understand the regulation of anti-Sm B cells Ig H chain transgenic (2-12H Tg) mice using the rearrangement from an anti-Sm B cell have been generated. Anti-Sm B cells are present in the spleens of non-autoimmune 2-12H Tg mice and most are transitional B cells. In addition, about30 percent of peritoneal B-l cells are anti-Sm in these mice. Although these mice respond to Sm immunization, indicating that tolerance is maintained by ignorance, pre-immune serum anti-Sm levels are no different from those of non-Tg mice. This is paradoxical, since B-l cells are responsible for most circulating IgM. In autoimmune MRL/lpr mice, anti-Sm B cells are activated but they do not differentiate to B-l. The three aims of this application test the following hypothesis: anti-Sm transitional B cells are driven by antigen to differentiate to B-1, but they are inhibited from activation by the expression of CD5, a negative regulator of B cell activation. In autoimmune mice, where differentiation to B-1 is blocked, anti-Sm B cells differentiate to B-2 where they are more readily activated. In the first aim, the ability of anti-Sm transitional, B cells to differentiate to B-1 will be determined by transfer of 2-12H Tg transitional. B cells to non-Tg mice. In addition, the V repertoires of anti-Sm transitional and B-1 cells of 212H Tg mice will be analyzed to determine whether differentiation to B-l is selective. In the second aim, anti-Sm B-1 cell function will be assessed in vitro and in vivo, and the role of CD5 determined in 2-12H Tg/CD54-/-mice. In the final aim, the fate of B cells that normally differentiate to B-l will be determined in autoimmune MRL/lpr mice using a Tg model system of B-l differentiation.