{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:30:55Z","timestamp":1792099855643,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"Objective<\/jats:title>Plasmablasts play important roles in autoimmune diseases, including systemic lupus erythematosus (SLE<\/jats:styled-content>). Activation of mechanistic target of rapamycin complex 1 (mTORC<\/jats:styled-content>1) is regulated by amino acid levels. In patients with SLE<\/jats:styled-content>, mTORC<\/jats:styled-content>1 is activated in B cells and modulates plasmablast differentiation. However, the detailed mechanisms of amino acid metabolism in plasmablast differentiation remain elusive. We undertook this study to evaluate the effects of methionine in human B cells.<\/jats:p><\/jats:sec>Methods<\/jats:title>Purified CD<\/jats:styled-content>19+ cells from healthy donors (n = 21) or patients with SLE<\/jats:styled-content> (n = 35) were cultured with Toll\u2010like receptor 7\/9 ligand, interferon\u2010\u03b1 (IFN<\/jats:styled-content>\u03b1), and B cell receptor crosslinking, and we determined the types of amino acids that were important for plasmablast differentiation and amino acid metabolism. We also identified the transcriptional regulatory mechanisms induced by amino acid metabolism, and we assessed B cell metabolism and its relevance to SLE<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>The essential amino acid methionine strongly committed cells to plasmablast differentiation. In the presence of methionine, Syk and mTORC<\/jats:styled-content>1 activation synergistically induced methyltransferase EZH<\/jats:styled-content>2 expression. EZH<\/jats:styled-content>2 induced H3K27me3 at BTB<\/jats:styled-content> and CNC<\/jats:styled-content> homolog 2 (Bach2) loci and suppressed Bach2 expression, leading to induction of B lymphocyte\u2013induced maturation protein 1 and X\u2010box binding protein 1 expression and plasmablast differentiation. CD<\/jats:styled-content>19+ cells from patients with SLE<\/jats:styled-content> overexpressed EZH<\/jats:styled-content>2, which was correlated with disease activity and autoantibody production.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings show that methionine activated signaling by controlling immunologic metabolism in B cells and played an important role in the differentiation of B cells into plasmablasts through epigenome modification of Bach2 by the methyltransferase EZH<\/jats:styled-content>2.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41208","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T07:38:37Z","timestamp":1579592317000},"page":"1143-1153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Methionine Commits Cells to Differentiate Into Plasmablasts Through Epigenetic Regulation of BTB<\/scp> and CNC<\/scp> Homolog 2 by the Methyltransferase 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