How different classes of the B cell antigen receptor (BCR) sense viral antigens used in vaccination protocols is poorly understood. Here, we study antigen binding and sensing of human Ramos B cells expressing a BCR of either the IgM or IgG1 class with specificity for the CD4-binding-site of the envelope (Env) protein of the HIV-1. Both BCRs carry an identical antigen binding site derived from the broad neutralizing antibody (bnAb) CH31. We find a five times higher expression of the IgG1-BCR in comparison to the IgM-BCR on the surface of transfected Ramos B cells. The two BCR classes also differ from each other in their interaction with cognate HIV Env antigens in that the IgG1-BCR and IgM-BCR bind preferentially to polyvalent and monovalent antigens, respectively. By generating an IgM/IgG1 chimeric BCR, we found that the class-specific BCR expression and antigen-sensing behavior can be transferred with the CH1γ domain from the IgG1-BCR to the IgM-BCR. Thus, the class of CH1 domain has an impact on BCR assembly and expression as well as on antigen sensing.

中文翻译：

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CH1 结构域影响 HIV 特异性 CH31 IgM-BCR 和 IgG-BCR 的表达和抗原感应


人们对不同类别的 B 细胞抗原受体 (BCR) 如何感知疫苗接种方案中使用的病毒抗原知之甚少。在这里，我们研究表达 IgM 或 IgG1 类 BCR 的人类 Ramos B 细胞的抗原结合和传感，并对 HIV-1 包膜 (Env) 蛋白的 CD4 结合位点具有特异性。两种 BCR 均携带源自广泛中和抗体 (bnAb) CH31 的相同抗原结合位点。我们发现转染的 Ramos B 细胞表面上 IgG1-BCR 的表达量是 IgM-BCR 的五倍。两种 BCR 类别在与同源 HIV Env 抗原的相互作用方面也存在差异，因为 IgG1-BCR 和 IgM-BCR 分别优先结合多价和单价抗原。通过生成 IgM/IgG1 嵌合 BCR，我们发现类特异性 BCR 表达和抗原感应行为可以通过 CH1γ 结构域从 IgG1-BCR 转移到 IgM-BCR。因此，CH1 结构域的类别对 BCR 组装和表达以及抗原感应有影响。