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

Journal of Neuroinflammation

Shuhei Sano¹  Daisuke Noto¹  Sachiko Miyake¹  Yasunobu Hoshino²  Yuji Tomizawa³  Nobutaka Hattori³  Kazumasa Yokoyama³ 

[1] Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-8421, Tokyo, Japan;Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-8421, Tokyo, Japan;Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan;Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan;

关键词: Neuromyelitis optica spectrum disorder;    Autoantibody;    B cells;    IL-2;   

DOI  :  10.1186/s12974-021-02375-w

来源: Springer

【 摘 要 】

BackgroundAnti-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.MethodsWe 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.ResultsThe 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.ConclusionsTo 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.

【 授权许可】

CC BY