Hydroxychloroquine efficiently suppresses inflammatory responses of human class-switched memory B cells via Toll-like receptor 9 inhibition

Clin Immunol. 2018 Oct;195:1-7. doi: 10.1016/j.clim.2018.07.003. Epub 2018 Jul 4.

Abstract

Hydroxychloroquine is widely used for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Although B cells contribute to the pathogenesis of these diseases, the action of hydroxychloroquine on B cells remains unclear. Here we examined the effects of hydroxychloroquine on functions of B cell subsets. Hydroxychloroquine efficiently inhibited the mammalian target of rapamycin complex 1, differentiation of CD19+IgD-CD27+ class-switched memory B cells to plasmablasts and their IgG production, under stimulation with CpG, a Toll-like receptor (TLR)-9 ligand. Hydroxychloroquine also inhibited CpG-induced production of interleukin-6 and tumor necrosis factor-α in B cell subsets. Taken together, hydroxychloroquine markedly suppresses the TLR9-mediated human B cell functions during inflammatory processes. Based on our results, we believe that hydroxychloroquine can be beneficial in the treatment of B cell-mediated autoimmune diseases.

Keywords: Human B cell; Hydroxychloroquine; Plasmablast; Toll-like receptor 9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Antibody Formation / drug effects
  • Antigens, CD19 / metabolism
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Humans
  • Hydroxychloroquine / pharmacology*
  • Immunoglobulin Class Switching
  • Immunologic Memory
  • Inflammation / drug therapy*
  • Interleukin-6 / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Toll-Like Receptor 9 / metabolism*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antigens, CD19
  • Interleukin-6
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factor-alpha
  • Hydroxychloroquine
  • MTOR protein, human
  • TOR Serine-Threonine Kinases