| First Author | Grenov A | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 5 | Pages | 110778 |
| PubMed ID | 35508130 | Mgi Jnum | J:325099 |
| Mgi Id | MGI:7283979 | Doi | 10.1016/j.celrep.2022.110778 |
| Citation | Grenov A, et al. (2022) YTHDF2 suppresses the plasmablast genetic program and promotes germinal center formation. Cell Rep 39(5):110778 |
| abstractText | Antibody-mediated immunity is initiated by B cell differentiation into multiple cell subsets, including plasmablast, memory, and germinal center (GC) cells. B cell differentiation trajectories are determined by transcription factors, yet very few mechanisms that specifically determine early B cell fates have been described. Here, we report a post-transcriptional mechanism that suppresses the plasmablast genetic program and promotes GC B cell fate commitment. Single-cell RNA-sequencing analysis reveals that antigen-specific B cell precursors at the pre-GC stage upregulate YTHDF2, which enhances the decay of methylated transcripts. Ythdf2-deficient B cells exhibit intact proliferation and activation, whereas differentiation into GC B cells is blocked. Mechanistically, B cells require YTHDF2 to attenuate the plasmablast genetic program during GC seeding, and transcripts of key plasmablast-regulating genes are methylated and bound by YTHDF2. Collectively, this study reveals how post-transcriptional suppression of gene expression directs appropriate B cell fate commitment during initiation of the adaptive immune response. |
