University of Washington School of Medicine and Seattle Children's Research Institute, Seattle, WA, USA; Translational Immunology, Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum München, Munich, Augsburg, Germany.
University Children's Hospital, Dr. von Haunersches Kinderspital, Ludwig Maximilian University, Munich, Germany; Translational Immunology, Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum München, Munich, Augsburg, Germany.
Clin Immunol. 2021 Jan;222:108638. doi: 10.1016/j.clim.2020.108638. Epub 2020 Dec 1.
To assess how B cell phenotype analysis correlates with antigen responses in patients with class switch recombination defects (CSRD) we quantified memory B cells by flow-cytometry and immunized CSRD patients with the neoantigen bacteriophage phiX174 (phage). CSRD patients showed uniformly absent or markedly reduced switched memory B cells (IgMIgDCD27). CD40L patients had reduced CD27 memory B cells (both non-switched and switched). In NEMO patients, results varied depending on the IKKγ gene variant. Three of four AID patients had normal percentages of CD27 memory B cells while CD27IgMIgD switched memory B cells were markedly reduced in all AID patients. Antibody response to phage was remarkably decreased with lack of memory amplification and class-switching in immunized CD40L, UNG deficient, and NEMO patients. Distinct B-cell phenotype pattern correlated with abnormal antibody responses to a T-cell dependent neoantigen, representing a powerful tool to identify CSRD patients.
为了评估在类别转换重组缺陷（CSRD）患者中，B 细胞表型分析与抗原反应的相关性，我们通过流式细胞术对记忆 B 细胞进行了定量分析，并使用新抗原噬菌体 phiX174（噬菌体）对 CSRD 患者进行了免疫。CSRD 患者表现出普遍缺失或明显减少的转换记忆 B 细胞（IgMIgDCD27）。CD40L 患者的 CD27 记忆 B 细胞减少（未转换和转换的均减少）。在 NEMO 患者中，结果因 IKKγ 基因变异而异。AID 患者中有 3 名患者的 CD27 记忆 B 细胞百分比正常，而所有 AID 患者的 CD27IgMIgD 转换记忆 B 细胞均明显减少。噬菌体的抗体反应显著降低，缺乏记忆扩增和免疫的 CD40L、UNG 缺陷和 NEMO 患者的类别转换。与 T 细胞依赖的新抗原异常抗体反应相关的独特 B 细胞表型模式，代表了识别 CSRD 患者的有力工具。
