| First Author | Haniuda K | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 5 | Pages | 108333 |
| PubMed ID | 33147467 | Mgi Jnum | J:346845 |
| Mgi Id | MGI:6716130 | Doi | 10.1016/j.celrep.2020.108333 |
| Citation | Haniuda K, et al. (2020) Metabolic Reprogramming Induces Germinal Center B Cell Differentiation through Bcl6 Locus Remodeling. Cell Rep 33(5):108333 |
| abstractText | The germinal center (GC) reaction is essential for long-lived humoral immunity. However, molecular requirements for the induction of Bcl6, the master regulator for GC B cell differentiation, remain unclear. Through screening for cytokines and other stimuli that regulate Bcl6 expression, we identify IL-4 as the strongest inducer. IL-4 signaling alters the metabolomic profile in activated B cells and induces accumulation of the TCA cycle intermediate alpha-ketoglutarate (alphaKG), which is required for activation of the Bcl6 gene locus. Mechanistically, after IL-4 treatment, STAT6 bound to the known enhancers in the Bcl6 locus recruits UTX, a demethylase for the repressive histone mark H3K27me3 that requires alphaKG as a cofactor. In turn, the H3K27me3 demethylation activates the enhancers and transcription of the Bcl6 gene. We propose that IL-4-mediated metabolic reprogramming in B cells is pivotal for epigenomic activation of Bcl6 expression to promote GC B cell differentiation. |
