Epitope-Specific Suppression of IgG Responses by Passively Administered Specific IgG: Evidence of Epitope Masking.
Epitope-Specific Suppression of IgG Responses by Passively Administered Specific IgG: Evidence of Epitope Masking.
复制标题
DOI：
10.3389/fimmu.2017.00238
复制
发表时间：
2017
影响因子：
7.3
通讯作者：
Heyman B
中科院分区：
文献类型：
--
作者：
Bergström JJ;Xu H;Heyman B
特异性免疫球蛋白与颗粒抗原一起被动注射，可完全阻止对该抗原的抗体反应。在缺乏Fcγ受体、补体因子1Q、C3或补体受体1和2的小鼠中，免疫球蛋白抑制绵羊红细胞抗体反应的能力是完整的，这表明Fc依赖的效应功能不参与。对这种抑制作用的两种最广泛讨论的解释是增加了对免疫球蛋白抗原复合体的清除和/或免疫球蛋白使抗原不被特定的B细胞识别，这就是所谓的表位掩蔽。关于免疫球蛋白如何引起抑制的大部分数据是通过研究免疫后第一周对分泌免疫球蛋白M的单个脾细胞的影响而获得的。在这里，我们表明，免疫球蛋白还抑制抗原特异性的卵泡外抗体分泌细胞、生发中心B细胞、长寿浆细胞、长期免疫球蛋白反应和记忆抗体反应的诱导。免疫球蛋白抗体可降低野生型小鼠脾中SRBC的数量，但不能降低FcγR缺陷小鼠脾中SRBC的数量。然而，没有观察到抑制与脾中SRBC的数量之间的相关性，这表明清除增加并不能解释免疫球蛋白介导的抑制。相反，我们发现了令人信服的表位掩蔽证据，因为与NP-SRBC一起注射的Ig G抗NP抑制了Ig G抗Np，但不抑制Ig G抗SRBC反应。反之亦然，NP-SRBC只抑制免疫球蛋白抗体的应答。总之，被动转移的免疫球蛋白抑制了抗原特异性抗体/B细胞反应的所有测量参数，一个重要的作用机制可能是表位掩蔽。
Specific IgG, passively administered together with particulate antigen, can completely prevent induction of antibody responses to this antigen. The ability of IgG to suppress antibody responses to sheep red blood cells (SRBCs) is intact in mice lacking FcγRs, complement factor 1q, C3, or complement receptors 1 and 2, suggesting that Fc-dependent effector functions are not involved. Two of the most widely discussed explanations for the suppressive effect are increased clearance of IgG–antigen complexes and/or that IgG “hides” the antigen from recognition by specific B cells, so-called epitope masking. The majority of data on how IgG induces suppression was obtained through studies of the effects on IgM-secreting single spleen cells during the first week after immunization. Here, we show that IgG also suppresses antigen-specific extrafollicular antibody-secreting cells, germinal center B-cells, long-lived plasma cells, long-term IgG responses, and induction of memory antibody responses. IgG anti-SRBC reduced the amount of SRBC in the spleens of wild-type, but not of FcγR-deficient mice. However, no correlation between suppression and the amount of SRBC in the spleen was observed, suggesting that increased clearance does not explain IgG-mediated suppression. Instead, we found compelling evidence for epitope masking because IgG anti-NP administered with NP-SRBC suppressed the IgG anti-NP, but not the IgG anti-SRBC response. Vice versa, IgG anti-SRBC administered with NP-SRBC, suppressed only the IgG anti-SRBC response. In conclusion, passively transferred IgG suppressed all measured parameters of an antigen-specific antibody/B cell response and an important mechanism of action is likely to be epitope masking.