CRI (CD35) As a Cellular Receptor for CIq

CRI (CD35) 作为 CIq 的细胞受体

• 批准号: 6711776
• 负责人: ANNE NICHOLSON-WELLER
• 金额: $ 43.45万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6711776
• 关键词: B lymphocyte; CD antigens; autoimmune disorder; binding proteins; biological signal transduction; chickens; clinical research; complement deficiency; complement receptor; human subject; immune complex; macrophage; mannose; monoclonal antibody; monocyte; neutrophil; patient oriented research; phagocytosis; receptor binding; recombinant proteins; tissue /cell culture

DESCRIPTION (provided by applicant): Clq and MBL participate in tissue remodeling by tagging apoptotic and necrotic tissue, respectively. Clq deficiency is associated with a 93% chance of developing a lupus-like syndrome characterized by an early onset of severe rash and nephritis with high morbidity and mortality. This striking association indicates an important role for Clq in the prevention of autoimmunity, which must depend upon interactions with Clq receptors, since the phenotypes of C4 and C2 deficiencies are much less severe. Our laboratories have demonstrated that Clq and MBL bind specifically to complement receptor 1 (CD35) on hematopoietic cells. Two hypotheses are proposed to link Clq deficiency and autoimmunity. First, Clq-dependent ligation of CD35 on B cells may evoke a negative signal that inhibits B cell proliferation. Second, Clq-dependent opsonization of apoptotic material and clearance by a CD35+ phagocyte prevents autoantigens from becoming immunogenic. The three aims of this proposal are: (1) To determine more precisely the binding site on CD35 for Clq and the binding site on Clq for CD35. (2) To define the functional consequences of Clq ligation of CD35 on leukocytes including the relevant signaling pathway utilized by CD35 on B cells and phagocytic cells. (3) To evaluate the ability of Clq-opsonized apoptotic material to be ingested via a CD35-mediated pathway and how cell surface calreticulin modulates this process. Although genetically determined Clq deficiency is a rare condition, it emphasizes the importance of Clq and its receptors. These studies of Clq receptor biology will provide insights into the pathogenesis of more common autoimmune diseases.

描述（由申请人提供）：Clq和MBL分别通过标记凋亡和坏死组织参与组织重塑。Clq缺乏与93%的机会发展成狼疮样综合征相关，其特征是早期发作的严重皮疹和肾炎，具有高发病率和死亡率。这种显著的关联表明Clq在预防自身免疫中的重要作用，这必须依赖于与Clq受体的相互作用，因为C4和C2缺陷的表型不那么严重。我们的实验室已经证明Clq和MBL特异性结合造血细胞上的补体受体1（CD35）。提出了两个假设，以链接Clq缺陷和自身免疫。首先，B细胞上的CD35的Clq依赖性连接可引起抑制B细胞增殖的负信号。第二，凋亡物质的Clq依赖性调理作用和CD35+吞噬细胞的清除防止自身抗原成为免疫原性的。本研究的三个目的是：（1）更精确地确定Clq在CD 35上的结合位点和Clq在CD 35上的结合位点。(2)确定白细胞上CD35的Clq连接的功能后果，包括B细胞和吞噬细胞上CD35利用的相关信号传导途径。(3)评估Clq调理的凋亡物质通过CD35介导的途径被摄取的能力以及细胞表面钙网蛋白如何调节该过程。虽然遗传决定的Clq缺乏症是一种罕见的情况，但它强调了Clq及其受体的重要性。Clq受体生物学的这些研究将提供更常见的自身免疫性疾病的发病机制的见解。