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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1622395

This article is part of the Research TopicModulating B Cell Subsets: Future Therapeutics for Autoimmune DiseasesView all articles

Exploring Immunological Alterations of B Cells in Peripheral Immunity via Single-Cell RNA Sequencing: Insights into Primary Membranous Nephropathy

Provisionally accepted
  • 1Nanjing Medical University, Nanjing, China
  • 2School of Life Science and Technology, China Pharmaceutical University, Nanjing, China

The final, formatted version of the article will be published soon.

Background: Primary Membranous Nephropathy (PMN) is characterized by dysregulated immune responses, with B cells playing critical roles in disease pathogenesis. However, the immunopathogenic mechanisms underlying B cell involvement in PMN remain elusive.We employed single-cell RNA sequencing on peripheral blood mononuclear cell samples (PBMC) obtained from 6 patients with PMN and 3 healthy controls (NC) to explore the transformation of B cells and their interaction with immune cells.Results: Compared with NC, the most significant alterations were in plasma cells and regulatory B (Breg) cells in PMN patients. Within plasma cells, Subcluster 0 was increased in PMN patients and exhibited enhanced autoimmunity. Breg subset B10 cells were elevated in PMN patients and displayed increased immune regulatory capacity, marked by enhanced cytokine and interleukin-10 production. B cell activating factor (BAFF) and galectin-9, which were secreted by CD14 monocyte, as potential regulators of plasma and Breg cells activity. Additionally, serum galectin-9 levels increased in PMN patients and showed a correlation with proteinuria and renal function in PMN.We reveal novel insights into the heterogeneity and functional diversity of B cells in patients with PMN. And revealed distinct roles for subgroup 0 plasma cells and B10 Breg cells in the pathogenesis of PMN. Furthermore, targeting B cells, such as galectin-9, presents promising opportunities for modulating the immune response in patients with PMN.

Keywords: ScRNA-seq, PBMC, PMN, galectin-9, B cell

Received: 03 May 2025; Accepted: 01 Aug 2025.

Copyright: © 2025 Lu, Chen, Guo, Li, Wu, Ying, Wu, Shu, Liu, Zhang, Mao, Xing, Liang, Duan and YUAN. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Hongwei Liang, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
Su yan Duan, Nanjing Medical University, Nanjing, China
Yanggang YUAN, Nanjing Medical University, Nanjing, China

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