Mettl14-mediated m6A modification is essential for germinal centre B cell response

The germinal centre (GC) response is essential for generating memory B and long-lived antibody-secreting plasma cells during T-cell-dependent immune response. In the GC, signals via B cell receptor (BCR) and CD40 collaboratively promote the proliferation and positive selection of GC B cells expressing BCRs with high affinities for specific antigens. Here, we show that methyltransferase like 14 (Mettl14)-mediated methylation of adenosines at the position N6 of mRNA (m6A) is essential for GC B cell response. Ablation of Mettl14 in B cells leads to compromised GC B cell proliferation and defective antibody response. Furthermore, 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 manner.