Lyubchenko Taras, Dal Porto Joseph M, Holers V Michael, Cambier John C
Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Denver, CO 802602, USA.
J Immunol. 2007 Sep 1;179(5):2695-9. doi: 10.4049/jimmunol.179.5.2695.
C3dg adducts of Ag can coligate complement receptor type 2 (CR2; CD21) and the B cell Ag receptor. This interaction significantly amplifies BCR-mediated signals in Ag-naive wild-type mice, lowering the threshold for B cell activation and the generation of humoral immune responses as much as 1000-fold. In this study we demonstrate that CR2-mediated complementation of BCR signals can also overcome B cell anergy. Unlike Ag alone, BCR/CR2 costimulation (Ars-CCG/C3dg complexes) of anergic Ars/A1 B cells led to Ca(2+) mobilization in vitro and the production of autoantibodies in vivo. Interestingly, the in vivo immune response of anergic cells occurs without the formation of germinal centers. These results suggest that the Ag unresponsiveness of anergic B cells can be overcome by cross-reactive (self-mimicking) Ags that have been complement-opsonized. This mechanism may place individuals exposed to complement-fixing bacteria at risk for autoimmunity.
银的C3dg加合物可连接2型补体受体（CR2；CD21）和B细胞抗原受体。这种相互作用在未接触过抗原的野生型小鼠中显著增强了BCR介导的信号，将B细胞活化和体液免疫反应的阈值降低了多达1000倍。在本研究中，我们证明CR2介导的BCR信号互补也能克服B细胞无反应性。与单独的抗原不同，无反应性的抗Ars/A1 B细胞的BCR/CR2共刺激（Ars-CCG/C3dg复合物）在体外导致Ca(2+)动员，并在体内产生自身抗体。有趣的是，无反应性细胞的体内免疫反应在没有生发中心形成的情况下发生。这些结果表明，已被补体调理的交叉反应性（自我模拟）抗原可克服无反应性B细胞的抗原无反应性。这种机制可能使接触补体结合细菌的个体面临自身免疫的风险。
