Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg 79104, Germany.
Faculty of Biology, Signalling Research Centers Centre for Integrative Biological Signalling Studies and Centre for Biological Signalling Studies, University of Freiburg, Freiburg 79104, Germany.
Proc Natl Acad Sci U S A. 2024 Jul 30;121(31):e2404728121. doi: 10.1073/pnas.2404728121. Epub 2024 Jul 23.
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.
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，目前了解甚少。在这里，我们研究了表达针对 HIV-1 包膜（Env）蛋白 CD4 结合位点的 IgM 或 IgG1 类 BCR 的人 Ramos B 细胞的抗原结合和感应，这两种 BCR 均带有源自广谱中和抗体（bnAb）CH31 的相同抗原结合位点。我们发现，转染的 Ramos B 细胞表面 IgG1-BCR 的表达比 IgM-BCR 高五倍。两种 BCR 类在与同源 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 CH1γ 结构域可以从 IgG1-BCR 转移到 IgM-BCR，从而转移类特异性 BCR 表达和抗原感应行为。因此，CH1 结构域的类别会影响 BCR 组装和表达以及抗原感应。
