Toapanta Franklin R, Ross Ted M
Department of Medicine, Division of Infectious Diseases, Center for Vaccine Research for Emerging Infections and Biodefense, University of Pittsburgh, School of Medicine Pittsburgh, PA 15261, USA.
Immunol Res. 2006;36(1-3):197-210. doi: 10.1385/IR:36:1:197.
C3d is the final degradation product of the third component of complement (C3). When conjugated to an antigen, C3d enhances immune responses to the fused antigen. Therefore, this molecule has been used as an adjuvant to enhance the immune responses to various foreign and self-proteins. C3d binds to the complement receptor 2 (CR2) that is located on the surface of follicular dendritic cells (FDC), B cells, and T cells in many species. C3d stimulates antigen presentation by FCD and helps to maintain immunological B cell memory. On B cells, C3d interaction with CR2 will collect molecules such as CD19, TAPA (CD81), and Lew 13. CD19 has a long intracellular tail that triggers a signaling cascade that results in cell activation and proliferation. Furthermore, simultaneous C3d-CR2 ligation and surface immunoglobulin (sIg) by antigen, activates two signaling pathways that cross-talk and synergize to activate B cells. However, C3d can enhance antibody titers in the absence of CR2 binding, indicating CR2-independent mechanism(s) of enhancement of the immune response. This review focuses on the complexity of the C3d-CR2 interaction, the importance of this interaction for the enhancement of the immune response by C3d and its derivatives, as well as the paradoxical enhancement of the immune response in the absence of CR2.
C3d是补体第三成分（C3）的最终降解产物。当与抗原结合时，C3d可增强对融合抗原的免疫反应。因此，该分子已被用作佐剂，以增强对各种外来蛋白和自身蛋白的免疫反应。C3d与补体受体2（CR2）结合，CR2存在于许多物种的滤泡树突状细胞（FDC）、B细胞和T细胞表面。C3d刺激FCD的抗原呈递，并有助于维持B细胞的免疫记忆。在B细胞上，C3d与CR2的相互作用会募集CD19、TAPA（CD81）和Lew 13等分子。CD19具有较长的细胞内尾巴，可触发信号级联反应，导致细胞活化和增殖。此外，抗原同时进行C3d-CR2连接和表面免疫球蛋白（sIg），可激活两条相互作用并协同激活B细胞的信号通路。然而，C3d在不结合CR2的情况下也能提高抗体滴度，这表明存在不依赖CR2的免疫反应增强机制。本综述重点关注C3d-CR2相互作用的复杂性、这种相互作用对C3d及其衍生物增强免疫反应的重要性，以及在没有CR2的情况下免疫反应的反常增强。
