Immune Netw.  2024 Aug;24(4):e25. 10.4110/in.2024.24.e25.

Mitochondria Activity and CXCR4 Collaboratively Promote the Differentiation of CD11c + B Cells Induced by TLR9 in Lupus

• Jang SH
• Shim JS
• Kim J
• Shin EG
• Yoon JH
• Lee LE
• Kwon HK
• Song JJ

• KMID: 2562612
• DOI: http://doi.org/10.4110/in.2024.24.e25

Abstract

Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c + B cells from lupus patients after ex vivo stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c + B cells in ODN-injected mice. Post-ex vivo ODN stimulation, we observed an increase in the proportion of CD11c^hi cells, with elevated mitochondrial activity and CXCR4 expression in CD11c + B cells from lupus patients. In vivo experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11c^hi B cells, leading to the generation of anti-dsDNA plasmablasts. The CXCR4 inhibitor AMD3100 and the mitochondrial complex I inhibitor IM156 significantly reduced the proportion of CD11c + B cells and autoreactive plasmablasts. These results underscore the pivotal roles of mitochondria and CXCR4 in the production of autoreactive plasmablasts.

Keyword

Systemic lupus erythematosus; B-Lymphocyte subsets; Mitochondria; CXCR4 receptor; TLR9 protein