Faust K B, Finke D, Klempt-Giessing K, Randers K, Zachrau B, Schlenke P, Kirchner H, Goerg S
Institute of Immunology and Transfusion Medicine, University of Luebeck, Luebeck, Germany.
Clin Exp Immunol. 2007 Oct;150(1):132-9. doi: 10.1111/j.1365-2249.2007.03456.x. Epub 2007 Jul 23.
Deficiencies in early complement components are associated with the development of systemic lupus erythematosus (SLE) and therefore early complement components have been proposed to influence B lymphocyte activation and tolerance induction. A defect in apoptosis is a potential mechanism for breaking of peripheral B cell tolerance, and we hypothesized that the lack of the early complement component C4 could initiate autoimmunity through a defect in peripheral B lymphocyte apoptosis. Previous studies have shown that injection of a high dose of soluble antigen, during an established primary immune response, induces massive apoptotic death in germinal centre B cells. Here, we tested if the antigen-induced apoptosis within germinal centres is influenced by early complement components by comparing complement C4-deficient mice with C57BL/6 wild-type mice. We demonstrate that after the application of a high dose of soluble antigen in wild-type mice, antibody levels declined temporarily but were restored almost completely after a week. However, after antigen-induced apoptosis, B cell memory was severely limited. Interestingly, no difference was observed between wild-type and complement C4-deficient animals in the number of apoptotic cells, restoration of antibody levels and memory response.
早期补体成分的缺陷与系统性红斑狼疮（SLE）的发生发展相关，因此有人提出早期补体成分会影响B淋巴细胞的活化和耐受性诱导。细胞凋亡缺陷是外周B细胞耐受性破坏的一种潜在机制，我们推测早期补体成分C4的缺乏可能通过外周B淋巴细胞凋亡缺陷引发自身免疫。先前的研究表明，在已建立的初次免疫反应期间注射高剂量可溶性抗原会诱导生发中心B细胞大量凋亡死亡。在此，我们通过比较补体C4缺陷小鼠和C57BL/6野生型小鼠，测试生发中心内抗原诱导的细胞凋亡是否受早期补体成分影响。我们证明，在野生型小鼠中应用高剂量可溶性抗原后，抗体水平暂时下降，但一周后几乎完全恢复。然而，抗原诱导的细胞凋亡后，B细胞记忆受到严重限制。有趣的是，野生型和补体C4缺陷动物在凋亡细胞数量、抗体水平恢复和记忆反应方面未观察到差异。
