| First Author | Wang Y | Year | 2024 |
| Journal | Immunity | Volume | 57 |
| Issue | 11 | Pages | 2547-2564.e12 |
| PubMed ID | 39476842 | Mgi Jnum | J:358428 |
| Mgi Id | MGI:7781229 | Doi | 10.1016/j.immuni.2024.10.004 |
| Citation | Wang Y, et al. (2024) Progressive polyadenylation and m6A modification of Ighg1 mRNA maintain IgG1 antibody homeostasis in antibody-secreting cells. Immunity 57(11):2547-2564.e12 |
| abstractText | Antigen-specific antibodies are generated by antibody-secreting cells (ASCs). How RNA post-transcriptional modification affects antibody homeostasis remains unclear. Here, we found that mRNA polyadenylations and N6-methyladenosine (m6A) modifications maintain IgG1 antibody production in ASCs. IgG heavy-chain transcripts (Ighg) possessed a long 3' UTR with m6A sites, targeted by the m6A reader YTHDF1. B cell-specific deficiency of YTHDF1 impaired IgG production upon antigen immunization through reducing Ighg1 mRNA abundance in IgG1(+) ASCs. Disrupting either the m6A modification of a nuclear-localized splicing intermediate Ighg1 or the nuclear localization of YTHDF1 reduced Ighg1 transcript stability. Single-cell RNA sequencing identified an ASC subset with excessive YTHDF1 expression in systemic lupus erythematosus patients, which was decreased upon therapy with immunosuppressive drugs. In a lupus mouse model, inhibiting YTHDF1-m6A interactions alleviated symptoms. Thus, we highlight a mechanism in ASCs to sustain the homeostasis of IgG antibody transcripts by integrating Ighg1 mRNA polyadenylation and m6A modification. |
