Department of Microbiology & Immunology, Faculty of Medicine and Health Sciences, McGill University, Montréal, Québec, Canada.
Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
Nat Commun. 2023 Nov 24;14(1):7682. doi: 10.1038/s41467-023-43504-8.
The efficacy of the B cell-targeting drug rituximab (RTX) in childhood idiopathic nephrotic syndrome (INS) suggests that B cells may be implicated in disease pathogenesis. However, B cell characterization in children with INS remains limited. Here, using single-cell RNA sequencing, we demonstrate that a B cell transcriptional program poised for effector functions represents the major immune perturbation in blood samples from children with active INS. This transcriptional profile was associated with an extrafollicular B cell response marked by the expansion of atypical B cells (atBCs), marginal zone-like B cells, and antibody-secreting cells (ASCs). Flow cytometry of blood from 13 children with active INS and 24 healthy donors confirmed the presence of an extrafollicular B cell response denoted by the expansion of proliferating RTX-sensitive extrafollicular (CXCR5) CD21 T-bet CD11c atBCs and short-lived T-bet ASCs in INS. Together, our study provides evidence for an extrafollicular origin for humoral immunity in active INS.
B 细胞靶向药物利妥昔单抗（RTX）在儿童特发性肾病综合征（INS）中的疗效表明 B 细胞可能参与疾病的发病机制。然而，INS 患儿的 B 细胞特征仍然有限。在这里，我们使用单细胞 RNA 测序表明，在处于活跃状态的 INS 患儿的血液样本中，一个准备好发挥效应功能的 B 细胞转录程序代表了主要的免疫失调。这种转录谱与滤泡外 B 细胞反应相关，其特征是不典型 B 细胞(atBC)、边缘区样 B 细胞和分泌抗体的细胞 (ASC) 的扩张。对 13 名处于活跃状态的 INS 患儿和 24 名健康供体的血液进行流式细胞术检测证实了滤泡外 B 细胞反应的存在，其特征是增殖的 RTX 敏感滤泡外（CXCR5）CD21 T-bet CD11c atBC 和寿命短的 T-bet ASC 在 INS 中扩张。综上所述，我们的研究为活跃期 INS 中体液免疫的滤泡外起源提供了证据。
