| First Author | Chen C | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 5 | Pages | 1437-1448 |
| PubMed ID | 29618490 | Mgi Jnum | J:261586 |
| Mgi Id | MGI:6155780 | Doi | 10.1084/jem.20171815 |
| Citation | Chen C, et al. (2018) Uhrf1 regulates germinal center B cell expansion and affinity maturation to control viral infection. J Exp Med 215(5):1437-1448 |
| abstractText | The production of high-affinity antibody is essential for pathogen clearance. Antibody affinity is increased through germinal center (GC) affinity maturation, which relies on BCR somatic hypermutation (SHM) followed by antigen-based selection. GC B cell proliferation is essentially involved in these processes; it provides enough templates for SHM and also serves as a critical mechanism of positive selection. In this study, we show that expression of epigenetic regulator ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) was markedly up-regulated by c-Myc-AP4 in GC B cells, and it was required for GC response. Uhrf1 regulates cell proliferation-associated genes including cdkn1a, slfn1, and slfn2 by DNA methylation, and its deficiency inhibited the GC B cell cycle at G1-S phase. Subsequently, GC B cell SHM and affinity maturation were impaired, and Uhrf1 GC B knockout mice were unable to control chronic virus infection. Collectively, our data suggest that Uhrf1 regulates GC B cell proliferation and affinity maturation, and its expression in GC B cells is required for virus clearance. |
