PHF14 is required for germinal center B cell development

Cell Immunol. 2020 Dec:358:104221. doi: 10.1016/j.cellimm.2020.104221. Epub 2020 Sep 28.

Abstract

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 (PHF14GCB KO) mice compared with the wild-type control (PHF14GCB WT) 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.

Keywords: Germinal center; PHF14; Proliferation; p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Proliferation / physiology
  • Cell Survival / physiology
  • Germinal Center / metabolism*
  • Immunity, Humoral / immunology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spleen / immunology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Phf14 protein, mouse
  • Transcription Factors