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

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 stimulation with a TLR9 agonist, Cp...

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Bibliographic Details
Published in:Immune network 2024-08, Vol.24 (4), p.9-22
Main Authors: Jang, Sung Hoon, Shim, Joo Sung, Kim, Jieun, Shin, Eun Gyeol, Yoon, Jong Hwi, Lee, Lucy Eunju, Kwon, Ho-Keun, Song, Jason Jungsik
Format: Article
Language:English
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Summary: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 stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c B cells in ODN-injected mice. Post- ODN stimulation, we observed an increase in the proportion of CD11c cells, with elevated mitochondrial activity and CXCR4 expression in CD11c B cells from lupus patients. experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11c 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.
ISSN:1598-2629
2092-6685
DOI:10.4110/in.2024.24.e25