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Title: Metabolic Reprogramming Commits Differentiation of Human CD27⁺IgD⁺ B Cells to Plasmablasts or CD27^-IgD^- Cells.
Author: Torigoe M, Iwata S, Nakayamada S, Sakata K, Zhang M, Hajime M, Miyazaki Y, Narisawa M, Ishii K, Shibata H, Tanaka Y.
Journal: J Immunol; 2017 Jul 15; 199(2):425-434. PubMed ID: 28626065.
Abstract:
B cells play a crucial role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). However, the relevance of the metabolic pathway in the differentiation of human B cell subsets remains unknown. In this article, we show that the combination of CpG/TLR9 and IFN-α markedly induced the differentiation of CD27⁺IgD⁺ unswitched memory B cells into CD27^hiCD38^hi plasmablasts. The response was accompanied by mammalian target of rapamycin complex 1 (mTORC1) activation and increased lactate production, indicating a shift to glycolysis. However, CpG alone induced the differentiation of unswitched memory B cells into CD27^-IgD^- memory B cells with high cytokine production, but such differentiation was suppressed by IFN-α. AMP-activated protein kinase activation enhanced the differentiation to CD27^-IgD^- B cells, but it attenuated mTORC1 activation and differentiation into plasmablasts. High mTORC1 activation was noted in CD19⁺ B cells of patients with SLE and correlated with plasmablast differentiation and disease activity. Taken together, differential metabolic reprogramming commits the differentiation of human unswitched memory B cells into plasmablasts (the combination of CpG and IFN-α amplifies mTORC1-glycolysis pathways) or CD27^-IgD^- memory B cells (CpG alone amplifies the AMP-activated protein kinase pathway). The former metabolic pathway may play a pivotal role in SLE.

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