Kayhan Basak, Aybay Cemalettin
Department of Immunology, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
Immunol Invest. 2004;33(4):367-83. doi: 10.1081/imm-200038675.
It has been known for a long time that passively administered antibodies (Abs) or immune complexes regulate the immune response to their specific antigen (Ag). IgG may sometimes suppress the humoral immune response against soluble antigens. The exact mechanism behind this phenomenon has not been understood yet and the requirement for the Fc part is still a matter of controversy. The present study was undertaken to clarify whether there is a true IgG-mediated Fc-dependent suppression of the immune response. Antigen and monoclonal antibody (mAb) used in this study were recombinant human interferon gamma (r-hIFN-gamma) and mouse monoclonal antibodies specific for human IFN-gamma [anti-hIFN-gamma mAb (CAy-IFNgamma38)] respectively. An intact IgG-free preparation of Fab plus various Fc fragments was prepared from papain-digested CAy-IFNgamma38. Ag/IgG and Ag/Fab complexes were prepared at various molar ratios. Keeping the Ag doses constant, mice were immunized either with Ag, Ag/IgG or Ag/Fab complexes. Primary immunization and the boosting were performed with the samples in complete and incomplete Freund's adjuvants respectively. Specific antibody levels were measured by an ELISA. Immunization performed with Ag/Fab complexes even at a molar ratio of 1:1.36 did not result in marked suppression of the response when compared to that of Ag only-immunization. In contrast, Ag/IgG complexes resulted in nearly 90% suppression of the antibody response. Our observations suggest that Fc part of IgG molecule plays a crucial role in suppression of the in vivo antibody response against the Ag when complexed with intact IgG.
长期以来人们都知道，被动给予的抗体（Abs）或免疫复合物会调节对其特定抗原（Ag）的免疫反应。IgG有时可能会抑制针对可溶性抗原的体液免疫反应。这一现象背后的确切机制尚未明了，且对于Fc部分的需求仍存在争议。本研究旨在阐明是否存在真正的IgG介导的Fc依赖性免疫反应抑制。本研究中使用的抗原和单克隆抗体（mAb）分别是重组人干扰素γ（r-hIFN-γ）和针对人IFN-γ的小鼠单克隆抗体[抗hIFN-γ mAb（CAy-IFNgamma38）]。从木瓜蛋白酶消化的CAy-IFNgamma38制备了完整的无IgG的Fab加各种Fc片段制剂。以各种摩尔比制备了Ag/IgG和Ag/Fab复合物。保持Ag剂量恒定，用Ag、Ag/IgG或Ag/Fab复合物免疫小鼠。初次免疫和加强免疫分别用完全和不完全弗氏佐剂中的样品进行。通过ELISA测量特异性抗体水平。与仅用Ag免疫相比，即使以1:1.36的摩尔比用Ag/Fab复合物进行免疫也不会导致反应的明显抑制。相反，Ag/IgG复合物导致抗体反应几乎90%的抑制。我们的观察结果表明，当与完整的IgG复合时，IgG分子的Fc部分在抑制针对Ag的体内抗体反应中起关键作用。
