| First Author | Huang H | Year | 2022 |
| Journal | J Immunol | Volume | 208 |
| Issue | 8 | Pages | 1924-1936 |
| PubMed ID | 35365563 | Mgi Jnum | J:325488 |
| Mgi Id | MGI:7281048 | Doi | 10.4049/jimmunol.2101071 |
| Citation | Huang H, et al. (2022) Mettl14-Mediated m6A Modification Is Essential for Germinal Center B Cell Response. J Immunol 208(8):1924-1936 |
| abstractText | The germinal center (GC) response is essential for generating memory B and long-lived Ab-secreting plasma cells during the T cell-dependent immune response. In the GC, signals via the BCR and CD40 collaboratively promote the proliferation and positive selection of GC B cells expressing BCRs with high affinities for specific Ags. Although a complex gene transcriptional regulatory network is known to control the GC response, it remains elusive how the positive selection of GC B cells is modulated posttranscriptionally. In this study, we show that methyltransferase like 14 (Mettl14)-mediated methylation of adenosines at the position N (6) of mRNA (N (6)-methyladenosine [m6A]) is essential for the GC B cell response in mice. Ablation of Mettl14 in B cells leads to compromised GC B cell proliferation and a defective Ab response. Interestingly, we unravel that Mettl14-mediated m6A regulates the expression of genes critical for positive selection and cell cycle regulation of GC B cells in a Ythdf2-dependent but Myc-independent manner. Furthermore, our study reveals that Mettl14-mediated m6A modification promotes mRNA decay of negative immune regulators, such as Lax1 and Tipe2, to upregulate genes requisite for GC B cell positive selection and proliferation. Thus, our findings suggest that Mettl14-mediated m6A modification plays an essential role in the GC B cell response. |
