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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2022

Open Access 01-12-2022 | Multiple Sclerosis | Research

Dysregulated B cell differentiation towards antibody-secreting cells in neuromyelitis optica spectrum disorder

Authors: Yasunobu Hoshino, Daisuke Noto, Shuhei Sano, Yuji Tomizawa, Kazumasa Yokoyama, Nobutaka Hattori, Sachiko Miyake

Published in: Journal of Neuroinflammation | Issue 1/2022

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Abstract

Background

Anti-aquaporin 4 (AQP4) antibody (AQP4-Ab) is involved in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). However, the mechanism involved in AQP4-Ab production remains unclear.

Methods

We analyzed the immunophenotypes of patients with NMOSD and other neuroinflammatory diseases as well as healthy controls (HC) using flow cytometry. Transcriptome analysis of B cell subsets obtained from NMOSD patients and HCs was performed. The differentiation capacity of B cell subsets into antibody-secreting cells was analyzed.

Results

The frequencies of switched memory B (SMB) cells and plasmablasts were increased and that of naïve B cells was decreased in NMOSD patients compared with relapsing–remitting multiple sclerosis patients and HC. SMB cells from NMOSD patients had an enhanced potential to differentiate into antibody-secreting cells when cocultured with T peripheral helper cells. Transcriptome analysis revealed that the profiles of B cell lineage transcription factors in NMOSD were skewed towards antibody-secreting cells and that IL-2 signaling was upregulated, particularly in naïve B cells. Naïve B cells expressing CD25, a receptor of IL-2, were increased in NMOSD patients and had a higher potential to differentiate into antibody-secreting cells, suggesting CD25+ naïve B cells are committed to differentiate into antibody-secreting cells.

Conclusions

To the best of our knowledge, this is the first study to demonstrate that B cells in NMOSD patients are abnormally skewed towards antibody-secreting cells at the transcriptome level during the early differentiation phase, and that IL-2 might participate in this pathogenic process. Our study indicates that CD25+ naïve B cells are a novel candidate precursor of antibody-secreting cells in autoimmune diseases.
Appendix
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Metadata
Title
Dysregulated B cell differentiation towards antibody-secreting cells in neuromyelitis optica spectrum disorder
Authors
Yasunobu Hoshino
Daisuke Noto
Shuhei Sano
Yuji Tomizawa
Kazumasa Yokoyama
Nobutaka Hattori
Sachiko Miyake
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-021-02375-w

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