Staphylococcus aureus peptidoglycan (PGN) induces pathogenic autoantibody production via autoreactive B cell receptor clonal selection, implications in systemic lupus erythematosus.
Staphylococcus aureus peptidoglycan (PGN) induces pathogenic autoantibody production via autoreactive B cell receptor clonal selection, implications in systemic lupus erythematosus.
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DOI：
10.1016/j.jaut.2022.102860
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发表时间：
2022-07
影响因子：
12.8
通讯作者：
Jiang, Wei
中科院分区：
文献类型：
--
作者：
Ning, Wangbin;Cheng, Da;Howe, Philip H.;Bian, Chuanxiu;Kamen, Diane L.;Luo, Zhenwu;Fu, Xiaoyu;Ogunrinde, Elizabeth;Yang, Liuqing;Wang, Xu;Li, Quan-Zhen;Oates, Jim;Zhang, Weiru;White, David;Wan, Zhuang;Gilkeson, Gary S.;Jiang, Wei
关键词：
ObjectivesThere is an intricate interplay between the microbiome and the immune response impacting development of normal immunity and autoimmunity. However, we do not fully understand how the microbiome affects production of natural-like and pathogenic autoantibodies. Peptidoglycan (PGN) is a component of the bacterial cell wall which is highly antigenic. PGNs from different bacteria can differ in their immune regulatory activities.MethodsC57BL/6 and MRL/lpr mice were intraperitoneally injected with saline or PGN fromStaphylococcus aureusorBacillus subtilis. Spleen anti-double-stranded DNA (dsDNA) IgG + B cells were sorted for B-cell receptor sequencing. Serum autoantibody levels and kidney damage were analyzed. Further, the association between plasmaS. aureustranslocation and systemic lupus erythematosus (SLE) pathogenesis was assessed in women.ResultsAdministration ofB. subtilisPGN induced natural-like anti-dsDNA autoantibodies (e.g., IgM, short lived IgG response, and no tissue damage), whereasS. aureusPGN induced pathogenic anti-dsDNA autoantibodies (e.g., prolonged IgG production, low IgM, autoantibody-mediated kidney damage) in C57BL/6 and/or MRL/lpr mice. However, serum total IgG did not differ.S. aureusPGN induced antibodies with reduced clonality and greater hypermutation of IGHV3-74 in splenic anti-dsDNA IgG + B cells from C57BL/6 mice. Further,S. aureusPGN promoted IgG class switch recombination via toll-like receptor 2. PlasmaS. aureusDNA levels were increased in women with SLE versus control women and correlated with levels of lupus-related autoantibodies and renal involvement.ConclusionsS. aureusPGN induces pathogenic autoantibody production, whereasB. subtilisPGN drives production of natural nonpathogenic autoantibodies.
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