关键词: B cell BCR CD4 binding site CH1 domain HIV-1 envelope

Mesh : Humans Immunoglobulin M / immunology Immunoglobulin G / immunology Receptors, Antigen, B-Cell / metabolism genetics immunology HIV-1 / immunology genetics B-Lymphocytes / immunology metabolism HIV Antibodies / immunology Protein Domains Antibodies, Neutralizing / immunology

来  源:   DOI:10.1073/pnas.2404728121   PDF(Pubmed)

Abstract:
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.
摘要:
对疫苗接种方案中使用的不同类别的B细胞抗原受体(BCR)对病毒抗原的感觉知之甚少。这里,我们研究了表达IgM或IgG1类BCR的人RamosB细胞对HIV-1包膜(Env)蛋白的CD4结合位点具有特异性的抗原结合和传感.两种BCR都携带源自广中和抗体(bnAb)CH31的相同抗原结合位点。我们发现在转染的RamosB细胞的表面上,IgG1-BCR的表达比IgM-BCR高五倍。两种BCR类别在与同源HIVEnv抗原的相互作用方面也彼此不同,因为IgG1-BCR和IgM-BCR优先结合多价和单价抗原,分别。通过生成IgM/IgG1嵌合BCR,我们发现类特异性BCR的表达和抗原敏感行为可以通过CH1γ结构域从IgG1-BCR转移到IgM-BCR。因此,CH1结构域的种类对BCR的组装和表达以及对抗原传感有影响。
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