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LSO-040 Mitochondria promotes autoimmune plasmablasts generation in lupus
  1. Sung Hoon Jang1,
  2. Joo Sung Shim1,
  3. Jieun Kim1,
  4. Ho-Keun Kwon2 and
  5. Jason Jungsik Song1
  1. 1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Republic of Korea
  2. 2Department of Microbiology, Yonsei University College of Medicine, Republic of Korea


Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the overproduction of autoantibodies. Recent studies showed that CD11c+ extrafollicular (EF) B-cells plays a central role for the development of lupus. We investigated the role of mitochondria in CD11c+ EF B cells and autoimmune plasmablasts in lupus.

Methods We investigated EF B cells, CD11c+ plasmablasts in B6 mice stimulated with CpG-Oligodeoxyribonucleotides (ODN) every other day for 10 days. Immune cell subtypes were analyzed by flow cytometry. Mitochondria membrane potential and mass were measured by JC-1, MTDR, and MTG. Generation of autoimmune plasmablasts were evaluated by measuring serum anti-dsDNA antibody by ELISA and anti-dsDNA antibody secreting cells by ELISPOT. Furthermore, mouse spleen B cells and human peripheral blood B cells from lupus patients were stimulated with CpG-ODN for 3 days and generation of EF B cells and mitochondria were evaluated by FACS. Mitochondria were inhibited by IM156 (complex I inhibitor), and CB-839 (GLS1 inhibitor) with in vivo or in vitro CpG-ODN stimulation.

Results In vivo injection of CpG-ODN induced anti-DNA antibody in mice. Mitochondria membrane potential and mass of EF B cells and plasmablasts were increased by CpG-ODN. Autoimmune plasmablasts measured by anti-dsDNA antibody ELISPOT were increased in bone marrow from CpG-ODN injected mice. CpG-ODN induced EF B cells and plasmablasts in in vitro culture condition with mouse splenic B cells and lupus B cells. Furthermore, CpG-ODN also increased mitochondria membrane potential and mass in in vitro culture condition. IM156 or CB-839 inhibited EF B cells and autoimmune plasmablasts in vivo and in vitro.

Conclusions This study demonstrated that the central role of mitochondria in generation of autoimmune plasmablasts in lupus. CpG-ODN induced autoimmune plasmablasts while IM156, or CB-839 inhibited autoimmune plasmablasts by suppression of mitochondria.

  • systemic lupus erythematosus
  • plasmablasts
  • mitochondria

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