Liao Yuheng, Hu Haofei, Wan Qijun, Song Haiying
Department of Nephrology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.
School of Medicine Shenzhen University, Shenzhen, China.
Front Immunol. 2025 Aug 7;16:1598197. doi: 10.3389/fimmu.2025.1598197. eCollection 2025.
B lymphocytes play a critical role in the pathogenesis of nephrotic syndrome (NS). This comprehensive review explores the phenotypic characteristics, pathogenic mechanisms, and clinical translational value of B cell subsets in different types of nephrotic syndrome. Studies demonstrate that B cells participate in disease development through multiple mechanisms, including autoantibody production, T cell function regulation, and cytokine secretion. In minimal change disease, B cell-mediated immune dysregulation is primarily characterized by decreased CD19+ cells and increased plasmablasts. Membranous nephropathy patients exhibit increased naïve B cells and decreased memory B cells, while focal segmental glomerulosclerosis is characterized by elevated class-switched memory B cells. These B cell subset alterations can serve as biomarkers for disease activity assessment and prognosis prediction. B cell-targeted therapies, such as anti-CD20 monoclonal antibodies, have demonstrated significant therapeutic efficacy in nephrotic syndrome, further confirming the pivotal role of B cells in its pathogenesis. Different pathological types of NS show significant differences in B cell subset changes, pathogenic mechanisms, and therapeutic responses. Primary and secondary nephrotic syndrome exhibit important distinctions in B cell activation mechanisms, subset imbalance patterns, degree of renal tissue infiltration, and autoantibody profiles. Age factors significantly influence B cell development, function, and therapeutic response, with notable differences between pediatric and adult patients in B cell subset distribution, treatment efficacy, and pharmacokinetics. With the application of emerging technologies such as single-cell sequencing, in-depth analysis of B cell subset characteristics and their interactions with other immune cells will provide new insights for developing more precise diagnostic and therapeutic strategies. However, current methodological heterogeneity challenges in research, including patient population differences, inconsistent B cell subset definitions, technical platform variations, and non-uniform clinical assessment criteria, limit the comparability of research results and clinical applications. Future efforts need to establish standardized B cell monitoring protocols and precision diagnostic systems, develop next-generation B cell-targeted therapeutic strategies, and deeply explore age-specific mechanisms and systems biology research to achieve precision medicine in nephrotic syndrome.
B淋巴细胞在肾病综合征（NS）的发病机制中起关键作用。这篇综述探讨了不同类型肾病综合征中B细胞亚群的表型特征、致病机制及临床转化价值。研究表明，B细胞通过多种机制参与疾病发展，包括自身抗体产生、T细胞功能调节和细胞因子分泌。在微小病变病中，B细胞介导的免疫失调主要表现为CD19+细胞减少和成浆细胞增加。膜性肾病患者表现为初始B细胞增加和记忆B细胞减少，而局灶节段性肾小球硬化的特征是类别转换记忆B细胞升高。这些B细胞亚群改变可作为疾病活动评估和预后预测的生物标志物。针对B细胞的疗法，如抗CD20单克隆抗体，在肾病综合征中已显示出显著的治疗效果，进一步证实了B细胞在其发病机制中的关键作用。不同病理类型的NS在B细胞亚群变化、致病机制和治疗反应方面存在显著差异。原发性和继发性肾病综合征在B细胞激活机制、亚群失衡模式、肾组织浸润程度和自身抗体谱方面表现出重要区别。年龄因素显著影响B细胞的发育、功能和治疗反应，儿童和成人患者在B细胞亚群分布、治疗效果和药代动力学方面存在显著差异。随着单细胞测序等新兴技术的应用，对B细胞亚群特征及其与其他免疫细胞相互作用的深入分析将为制定更精确的诊断和治疗策略提供新见解。然而，当前研究中存在的方法学异质性挑战，包括患者群体差异、B细胞亚群定义不一致、技术平台差异和临床评估标准不统一，限制了研究结果的可比性和临床应用。未来需要建立标准化B细胞监测方案和精准诊断系统，开发下一代针对B细胞的治疗策略，并深入探索年龄特异性机制和系统生物学研究，以实现肾病综合征的精准医学。
