Complement deficiency and environment in autoimmunity

描述（由申请人提供）：系统性红斑狼疮（SLE）是一种破坏性的自身免疫性疾病，其特征是产生自身抗体，抗smith （Sm）是该疾病最特异性的抗体。SLE的病因已知有显著的遗传和环境因素。补体系统的大量数据链缺陷与自身免疫性疾病的发展，特别是SLE。在小鼠中，补体蛋白C4或补体受体CR2 （CD21）的缺乏都会引发sle样疾病的发生。在人类中，部分或完全C4缺乏强烈地诱发SLE，并且最近在人类SLE患者中观察到CD21表达降低。补体中的这些遗传缺陷如何与环境效应物相互作用而引发疾病尚不清楚。我们将缺乏C4或CD21的小鼠与表达Sm特异性Ig重链的转基因系杂交。我们建议研究环境应激源对这些小鼠抗sm B细胞的影响以及抗sm抗体的产生，以阐明SLE发展中遗传和环境因素之间的相互作用。

DESCRIPTION (provided by applicant): Systemic lupus erythematosus (SLE) is a devastating autoimmune disease marked by the production of autoantibodies, anti-Smith (Sm) being the most specific for the disease. The etiology of SLE is known to have significant genetic and environmental components. Abundant data link deficiencies of the complement system to the development of autoimmune diseases, particularly SLE. Deficiencies of either complement protein C4 or the complement receptor CR2 (CD21) trigger development of SLE-like disease in mice. Partial or complete C4 deficiency strongly predisposes to SLE in humans, and recently, decreased CD21 expression has been observed in human SLE patients. How these genetic deficiencies in complement interact with environmental effectors to trigger disease is unknown. We have crossed mice deficient for C4 or CD21 to a transgenic line which expresses an Ig heavy-chain specific for Sm. We propose to study the effect of environmental stressors on anti-Sm B cells and the development of anti-Sm antibodies in these mice to elucidate the interplay between genetic and environmental components of SLE development.