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Uhrf1 regulates germinal center B cell expansion and affinity maturation to control viral infection.


ABSTRACT: 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.

SUBMITTER: Chen C 

PROVIDER: S-EPMC5940267 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Uhrf1 regulates germinal center B cell expansion and affinity maturation to control viral infection.

Chen Chao C   Zhai Sulan S   Zhang Le L   Chen Jingjing J   Long Xuehui X   Qin Jun J   Li Jianhua J   Huo Ran R   Wang Xiaoming X  

The Journal of experimental medicine 20180404 5


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 a  ...[more]

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