B细胞激活因子
细胞生物学
生物
受体
磷酸化
信号转导
生物化学
免疫学
B细胞
抗体
作者
Melissa Lempicki,Saikat Kumar Paul,Vlad Serbulea,Clint Upchurch,Srabani Sahu,Jake A. Gray,Gorav Ailawadi,Brandon L. Garcia,Coleen A. McNamara,Norbert Leitinger,Akshaya K. Meher
标识
DOI:10.1016/j.cellimm.2022.104603
摘要
Human recombinant B cell activating factor (BAFF) is secreted as 3-mers, which can associate to form 60-mers in culture supernatants. However, the presence of BAFF multimers in humans is still debated and it is incompletely understood how BAFF multimers activate the B cells. Here, we demonstrate that BAFF can exist as 60-mers or higher order multimers in human plasma. In vitro, BAFF 60-mer strongly induced the transcriptome of B cells which was partly attenuated by antagonism using a soluble fragment of BAFF receptor 3. Furthermore, compared to BAFF 3-mer, BAFF 60-mer strongly induced a transient classical and prolonged alternate NF-κB signaling, glucose oxidation by both aerobic glycolysis and oxidative phosphorylation, and succinate utilization by mitochondria. BAFF antagonism selectively attenuated classical NF-κB signaling and glucose oxidation. Altogether, our results suggest critical roles of BAFF 60-mer and its BAFF receptor 3 binding site in hyperactivation of B cells.
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