Key Points A threshold of epitope density for a self-antigen elicits IgG1, IgG2b, and IgG3. The class-switched autoreactive Abs were induced in the absence of T cell help. Epitope density has a profound impact on B cell responses to particulate Ags, the molecular mechanisms of which remain to be explored. To dissect the role of epitope density in this process, we have synthesized a series of liposomal particles, similar to the size of viruses, that display a model self-antigen peptide at defined surface densities. Immunization of C57BL/6J mice using these particles elicited both IgM and class-switched IgG1, IgG2b, and IgG3 autoreactive Abs that depended on the epitope density. In C57BL/6 gene knockout mice lacking either functional TCRs or MHC class II molecules on B cells, the liposomal particles also elicited IgM, IgG1, IgG2b, and IgG3 responses that were comparable in magnitudes to wild-type mice, suggesting that this B cell response was independent of cognate T cell help. Notably, the titer of the IgG in wild-type animals could be increased by more than 200-fold upon replacement of liposomes with bacteriophage Qβ virus-like particles that displayed the same self-antigen peptide at comparable epitope densities. This enhancement was lost almost completely in gene knockout mice lacking either TCRs or MHC class II molecules on B cells. In conclusion, epitope density above a threshold on particulate Ags can serve as a stand-alone signal to trigger secretion of autoreactive and class-switched IgG in vivo in the absence of cognate T cell help or any adjuvants. The extraordinary immunogenicity of Qβ viral-like particles relies, in large part, on their ability to effectively recruit T cell help after B cell activation.

中文翻译：

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在表位密度阈值以上的脂质体纳米颗粒上显示的自身抗原会引发类别转换的自身反应性抗体，独立于 T 细胞帮助

要点 自身抗原的表位密度阈值引发 IgG1、IgG2b 和 IgG3。在没有 T 细胞帮助的情况下诱导了类别转换的自身反应性抗体。表位密度对 B 细胞对微粒 Ag 的反应具有深远的影响，其分子机制仍有待探索。为了剖析表位密度在该过程中的作用，我们合成了一系列类似于病毒大小的脂质体颗粒，它们以定义的表面密度显示模型自身抗原肽。使用这些颗粒对 C57BL/6J 小鼠进行免疫接种会引发 IgM 和类别转换的 IgG1、IgG2b 和 IgG3 自身反应性抗体，这取决于表位密度。在 B 细胞上缺乏功能性 TCR 或 MHC II 类分子的 C57BL/6 基因敲除小鼠中，脂质体颗粒也引发 IgM、IgG1、IgG2b、和 IgG3 反应的幅度与野生型小鼠相当，表明这种 B 细胞反应独立于同源 T 细胞的帮助。值得注意的是，在用噬菌体 Qβ 病毒样颗粒替代脂质体后，野生型动物中 IgG 的滴度可提高 200 倍以上，该颗粒以可比的表位密度展示相同的自身抗原肽。在 B 细胞上缺乏 TCR 或 MHC II 类分子的基因敲除小鼠中，这种增强几乎完全丧失。总之，在没有同源 T 细胞帮助或任何佐剂的情况下，高于颗粒 Ag 阈值的表位密度可以作为独立信号触发体内自身反应性和类别转换 IgG 的分泌。Qβ 病毒样颗粒非凡的免疫原性在很大程度上依赖于