Functional impairment of CD19+CD24hiCD38hi B cells in neuromyelitis optica spectrum disorder is restored by B cell depletion therapy

Yeseul Kim, So Yeon Kim, Sang Min Han, Rosah May Payumo, Kevin Park, Ha Eun Kim, Su Hyun Kim, Jae Won Hyun, Eunjig Lee, Ho Jin Kim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


The role of B cells in immune response regulation is context dependent. In some cases, bystander B cell activation leads to interleukin-10 (IL-10) production, suppressing inappropriate immune responses. However, the role of B cells in regulation of autoimmune diseases, including neuromyelitis optica spectrum disorder (NMOSD), is incompletely understood. NMOSD is an autoimmune disease of the central nervous system with a relapsing-remitting course in which acute attacks lead to severe disability. B cell depletion therapy (BCDT) has shown clinical efficacy in NMOSD by eliminating pathogenic B cells; however, its effect on regulatory B (Breg) cells remains elusive. Here, we evaluated the B cell subsets, Breg cell function, and the effect of BCDT on these cells in patients with NMOSD. We showed that CD24hiCD38hi B cells from patients with NMOSD did not inhibit CD4+ T cell production of interferon-γ (IFN-γ), IL-17, or IL-21 and failed to inhibit follicular helper T cell expansion or induce regulatory T cells. This cellular impairment in patients with NMOSD can be explained by deficient Breg cell numbers and Breg cell-intrinsic deficits in IL-10 production specifically in response to B cell bystander activation. Using cross-sectional and 3-year longitudinal studies, we showed that BCDT treatment restored the numerical deficiency of Breg cells. Moreover, the post-BCDT repopulated CD24hiCD38hi B cells restored IL-10 production and suppressed IFN-γ and IL-17 production by CD4+ T cells. Our results suggest that both numerical deficiency of CD24hiCD38hi B cells and their impaired regulatory function contribute to NMOSD pathophysiology, and function is restored after BCDT.

Original languageEnglish
Article numberabk2132
JournalScience Translational Medicine
Issue number623
Publication statusPublished - 2021 Dec 8

Bibliographical note

Publisher Copyright:
© 2021 The Authors.

All Science Journal Classification (ASJC) codes

  • Medicine(all)


Dive into the research topics of 'Functional impairment of CD19+CD24hiCD38hi B cells in neuromyelitis optica spectrum disorder is restored by B cell depletion therapy'. Together they form a unique fingerprint.

Cite this