Chi Ma, FuKun W Hoffmann, Ashley E Shay, Imhoi Koo, Kathy A Green, William R Green, Peter R Hoffmann
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Lipid peroxidation was measured and found to increase ∼2-fold in KO vs. wild-type (WT) B cells. Cell death was not impacted by KO in LPS-treated B cells and proliferation was only slightly reduced, but differentiation into CD138 + Blimp-1+ plasma B cells was decreased ∼2-fold. This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. Overall, these findings detail the lipidomic response of B cells to LPS activation and reveal the importance of upregulated SELENOI for promoting differentiation into IgM-secreting plasma B cells.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212798/pdf/","citationCount":"0","resultStr":"{\"title\":\"Upregulated selenoprotein I during lipopolysaccharide-induced B cell activation promotes lipidomic changes and is required for effective differentiation into IgM-secreting plasma B cells.\",\"authors\":\"Chi Ma, FuKun W Hoffmann, Ashley E Shay, Imhoi Koo, Kathy A Green, William R Green, Peter R Hoffmann\",\"doi\":\"10.1093/jleuko/qiae024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The mechanisms driving metabolic reprogramming during B cell activation are unclear, particularly roles for enzymatic pathways involved in lipid remodeling. 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This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. 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引用次数: 0
摘要
B细胞活化过程中代谢重塑的驱动机制尚不清楚,尤其是参与脂质重塑的酶通路的作用。我们发现,用脂多糖(LPS)激活小鼠 B 细胞会导致总脂质增加 1.6 倍,其中包括更高水平的磷脂酰乙醇胺(PE)和磷脂酰 PE。硒蛋白 I(SELENOI)是一种[62] 乙醇胺磷脂转移酶,参与 PE 和磷脂酰 PE 的合成。SELENOI基因敲除(KO)的B细胞表现出塑门冬酰胺基PE水平的下降,而塑门冬酰胺基PE具有重要的抗氧化作用。对脂质过氧化进行测量后发现,KO 与 WT B 细胞相比,脂质过氧化增加了 2 倍。在 LPS 处理的 B 细胞中,细胞死亡不受 KO 的影响,增殖也只是略有减少,但分化成 CD138 + Blimp-1+ 浆 B 细胞的数量减少了 2 倍。这导致了对识别配体 B 细胞活化因子(BAFF)的 B 细胞分化重要受体的检测,与 WT 对照组相比,KO B 细胞上跨膜活化剂和钙调节剂及细胞嗜蛋白配体相互作用因子(TACI;CD267)的水平显著下降。与 WT 小鼠相比,接种卵清蛋白(OVA)/佐剂会导致 KO 小鼠血清中的 OVA 特异性 IgM 水平下降。实时 PCR 分析表明,在接种疫苗或 LP-BM5 逆转录病毒感染的诱导下,KO 小鼠脾脏中表面 IgM 向分泌型 IgM 的转换减少。总之,这些发现详细说明了 B 细胞对 LPS 激活的脂质体反应,并揭示了上调的 SELENOI 对促进分化为分泌 IgM 的浆 B 细胞的重要性。
Upregulated selenoprotein I during lipopolysaccharide-induced B cell activation promotes lipidomic changes and is required for effective differentiation into IgM-secreting plasma B cells.
The mechanisms driving metabolic reprogramming during B cell activation are unclear, particularly roles for enzymatic pathways involved in lipid remodeling. We found that murine B cell activation with lipopolysaccharide (LPS) led to a 1.6-fold increase in total lipids that included higher levels of phosphatidylethanolamine (PE) and plasmenyl PE. Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase involved in the synthesis of both PE and plasmenyl PE, and SELENOI expression was also upregulated during activation. Selenoi knockout (KO) B cells exhibited decreased levels of plasmenyl PE, which plays an important antioxidant role. Lipid peroxidation was measured and found to increase ∼2-fold in KO vs. wild-type (WT) B cells. Cell death was not impacted by KO in LPS-treated B cells and proliferation was only slightly reduced, but differentiation into CD138 + Blimp-1+ plasma B cells was decreased ∼2-fold. This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. Overall, these findings detail the lipidomic response of B cells to LPS activation and reveal the importance of upregulated SELENOI for promoting differentiation into IgM-secreting plasma B cells.
期刊介绍:
JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.