Generation of a novel CD30+ B cell subset producing GM-CSF and its possible link to the pathogenesis of systemic sclerosis

K. Higashioka, Y. Kikushige, M. Ayano, Y. Kimoto, H. Mitoma, M. Kikukawa, M. Akahoshi, Y. Arinobu, T. Horiuchi, K. Akashi, H. Niiro

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Systemic sclerosis (SSc) is a T helper type 2 (Th2)-associated autoimmune disease characterized by vasculopathy and fibrosis. Efficacy of B cell depletion therapy underscores antibody-independent functions of B cells in SSc. A recent study showed that the Th2 cytokine interleukin (IL)-4 induces granulocyte–macrophage colony-stimulating factor (GM-CSF)-producing effector B cells (GM-Beffs) in humans. In this study, we sought to elucidate the generation mechanism of GM-Beffs and also determine a role of this subset in SSc. Among Th-associated cytokines, IL-4 most significantly facilitated the generation of GM-Beffs within memory B cells in healthy controls (HCs). In addition, the profibrotic cytokine transforming growth factor (TGF)-β further potentiated IL-4- and IL-13-induced GM-Beffs. Of note, tofacitinib, a Janus kinase (JAK) inhibitor, inhibited the expression of GM-CSF mRNA and protein in memory B cells induced by IL-4, but not by TGF-β. GM-Beffs were enriched within CD20+CD30+CD38−/low cells, a distinct population from plasmablasts, suggesting that GM-Beffs exert antibody-independent functions. GM-Beffs were also enriched in a CD30+ fraction of freshly isolated B cells. GM-Beffs generated under Th2 conditions facilitated the differentiation from CD14+ monocytes to DC-SIGN+CD1a+CD14CD86+ cells, which significantly promoted the proliferation of naive T cells. CD30+ GM-Beffs were more pronounced in patients with SSc than in HCs. A subpopulation of SSc patients with the diffuse type and concomitant interstitial lung disease exhibited high numbers of GM-Beffs. Together, these findings suggest that human GM-Beffs are enriched in a CD30+ B cell subset and play a role in the pathogenesis of SSc.

Original languageEnglish
Pages (from-to)233-243
Number of pages11
JournalClinical and Experimental Immunology
Volume201
Issue number3
DOIs
Publication statusPublished - Sept 1 2020

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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