Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjin 211166, China; Analysis Center, Nanjing Medical University, Nanjing 211166, China.
Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjin 211166, China.
Cell Immunol. 2020 Dec;358:104221. doi: 10.1016/j.cellimm.2020.104221. Epub 2020 Sep 28.
Germinal centers (GCs), which are the site of antibody diversification and affinity maturation, are vitally important for humoral immunity. GC B cell proliferation is essentially for these processes by providing enough templates for somatic hypermutation (SHM) and serving as a critical mechanism of positive selection. In the current study, we found a significant reduction of GC response in the spleens of GC B cell specific PHF14 knockout (PHF14) mice compared with the wild-type control (PHF14) when the mice were challenged with SRBCs or lymphocytic choriomeningitis virus. We also demonstrated that PHF14 did not affect the cell survival of GC B cells, but regulated the proliferation of GC B cells. In addition, PHF14 suppressed the expression of Cdkn1a (p21) though regulating the level of H3K4me3 to control the proliferation of GC B cells. Collectively, our data suggest that PHF14 plays an important role in the process of germinal center formation by regulating GC B cell proliferation in spleen.
生发中心(GCs)是抗体多样化和亲和力成熟的场所,对体液免疫至关重要。GC B 细胞增殖通过为体细胞超突变(SHM)提供足够的模板并作为阳性选择的关键机制,为这些过程提供了基本条件。在本研究中,我们发现当用 SRBC 或淋巴细胞性脉络丛脑膜炎病毒攻击时,GC B 细胞特异性 PHF14 敲除(PHF14)小鼠脾脏中的 GC 反应明显低于野生型对照(PHF14)。我们还证明 PHF14 不影响 GC B 细胞的细胞存活,但调节 GC B 细胞的增殖。此外,PHF14 通过调节 H3K4me3 的水平抑制 Cdkn1a(p21)的表达,从而控制 GC B 细胞的增殖。总之,我们的数据表明 PHF14 通过调节脾脏中 GC B 细胞的增殖在生发中心形成过程中发挥重要作用。