B Cell Superantigen Immune Complex Tissue Inflammation

与常规抗原不同，B细胞超抗原（B细胞SAg）结合免疫球蛋白的Fab B区 (Ig)互补决定区以外的分子。这些非传统的抗原可以 与大量宿主的外周B细胞和血清免疫球蛋白结合 与整个可变区重链（VH）或可变区轻链（VL）基因的许多成员相互作用 家人例如，由厌氧菌株Peptostreptococcusmagnus分泌的蛋白质L与厌氧菌株Peptostreptococcusmagnus反应。 大多数人Vk 1+、Vk 3+和Vk 4 + Ig以及同源鼠Vk+ Ig的Fab。B细胞SAgs 与大量血清IgG结合强调了它们引起免疫复合物介导的组织免疫的潜力。 损伤在本申请中提出的研究的总体目标是阐明细胞和细胞内的蛋白质。 肺中B细胞SAg诱导的免疫复合物介导的炎症的分子发病机制。的 具体目标是确定由B细胞SAg，蛋白L， 1)证明免疫复合物组织损伤的组织病理学相关性，2）需要与 选择性Vk Ig和3）由参与常规免疫调节的细胞/促炎介质协调。 抗原/抗体复合物介导的组织损伤。这些目标将通过使用小鼠品系进行检查 通过基因操作来分离感兴趣的因子。由于迄今为止描述的大多数B细胞SAg 来自无处不在的微生物，这些研究的信息可能会提供深入了解 感染因子促进免疫复合物介导的免疫复合物介导的 风湿性和自身免疫性疾病。

B cell superantigens (B cell SAgs), unlike conventional antigens, bind to the Fab regions of immunoglobulin (Ig) molecules outside their complementarity determining regions. These unconventional antigens can react with a substantial amount of a host's peripheral B cells and serum immunoglobulins by virtue of their ability to interact with many members of an entire variable region heavy (VH) or variable region light (VL)gene family. For example, protein L, secreted by the anaerobic strain Peptostreptococcusmagnus, reacts with the Fabs of most human Vk1+, Vk3+, and Vk4+ Igs and homologous murine Vk+ Igs. The ability of B cell SAgs to bind to a large amount of serum IgG underscores their potential to cause imune complex-mediatedtissue injury. The overall objective of the studies proposed in this application is to elucidate the cellular and molecular pathogenesis of B cell SAg-induced immune complex-mediated inflammation in the lung. The specific goals are to determine whether lung inflammation induced by the B cell SAg, protein L, 1) demonstrates histopathological correlates of immune complex tissue injury, 2) requires the interaction with selective Vk Igs and 3) is orchestrated by cells/proinflammatory mediators involved in conventional antigen/antibody complex-mediated tissue injury. These objectives will be examined by using mouse strains manipulated genetically to isolate the factors of interest. Since most of the B cell SAgs described to date are derived from ubiquitous microbes, information from these studies will likely provide insight into mechanisms by which infectious agents contribute to the pathogenesis of immune complex-mediated rheumatic and autoimmune disorders.