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<p>The NF-κB family comprises five transcription factors (RELA, RELB, C-REL, NF-κB1 (p50) and NF-κB2 (p52)) that form homo- or heterodimers among themselves to regulate gene expression by binding DNA. Here we show that p52 activates transcription without directly binding DNA but as a heterotetrameric complex with ETS1, a transcription factor outside the NF-κB family. By generating a knock-in mouse model (<i>Nfkb2</i><sup>ki/ki</sup>) with three mutated residues on p52 required for its interaction with ETS1, but not RELB, we demonstrate that the p52–ETS1 complex regulates the expression of transcription factors OCT1 and OBF1, which are known to be critical for the germinal center program. Consequently, B cell-intrinsic expression of the p52–ETS1 complex was indispensable for splenic germinal center B cell formation and T cell-dependent antibody responses. Functionally, loss of p52–ETS1 interaction led to diminished antigen-specific IgE, thereby protecting mice from allergic responses. Collectively, our findings expand current knowledge of NF-κB signaling and may provide new therapeutic targets for the treatment of allergic diseases.</p>

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The transcription complex p52–ETS1 is essential for germinal center formation

  • 期刊论文

  • 发表日期：

    2025年7月25日

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  • Dhakshayini Morgan,
  • Biyan Zhang,
  • Kerem Fidan,
  • Wenfai Pan,
  • Thamil Selvan Vaiyapuri,
  • Anandhkumar Raju,
  • Dorcas Hei,
  • Ting Yi See,
  • Ita Novita Sari,
  • Jun Wei Chan,
  • Prativa Majee,
  • Akhila Balachander,
  • Jiabo Yu,
  • Ada Hang-Heng Wong,
  • Michelle Meng Huang Mok,
  • Shi Hui Foo,
  • Wei Lin Tang,
  • Nicholas Ang,
  • Ivan Tan,
  • Yan Fen Peng,
  • Patrick Jaynes,
  • Shengli Xu,
  • Gourisankar Ghosh,
  • Shandy Shahabi,
  • Anand D. Jeyasekharan,
  • Masahito Ikawa,
  • Yongliang Zhang,
  • Shanshan Wu Howland,
  • Mai Chan Lau,
  • Vivien Ya-Fan Wang,
  • Kong-Peng Lam,
  • Vinay Tergaonkar

摘要

The NF-κB family comprises five transcription factors (RELA, RELB, C-REL, NF-κB1 (p50) and NF-κB2 (p52)) that form homo- or heterodimers among themselves to regulate gene expression by binding DNA. Here we show that p52 activates transcription without directly binding DNA but as a heterotetrameric complex with ETS1, a transcription factor outside the NF-κB family. By generating a knock-in mouse model (Nfkb2ki/ki) with three mutated residues on p52 required for its interaction with ETS1, but not RELB, we demonstrate that the p52–ETS1 complex regulates the expression of transcription factors OCT1 and OBF1, which are known to be critical for the germinal center program. Consequently, B cell-intrinsic expression of the p52–ETS1 complex was indispensable for splenic germinal center B cell formation and T cell-dependent antibody responses. Functionally, loss of p52–ETS1 interaction led to diminished antigen-specific IgE, thereby protecting mice from allergic responses. Collectively, our findings expand current knowledge of NF-κB signaling and may provide new therapeutic targets for the treatment of allergic diseases.