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A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation

Author

Listed:
  • Jianfeng Wu

    (Xiamen University
    Xiamen University)

  • Kang Yang

    (Xiamen University)

  • Shaowei Cai

    (Xiamen University)

  • Xiaohan Zhang

    (Xiamen University)

  • Lichen Hu

    (Xiamen University)

  • Fanjia Lin

    (Xiamen University)

  • Su-qin Wu

    (Xiamen University)

  • Changchun Xiao

    (Xiamen University)

  • Wen-Hsien Liu

    (Xiamen University)

  • Jiahuai Han

    (Xiamen University
    Xiamen University
    Cancer Research Center of Xiamen University, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University)

Abstract

Plasma cells (PC) are antibody-secreting cells and terminal effectors in humoral responses. PCs differentiate directly from activated B cells in response to T cell-independent (TI) antigens or from germinal center B (GCB) cells in T cell-dependent (TD) antigen-induced humoral responses, both of which pathways are essentially regulated by the transcription factor BLIMP1. The p38 mitogen-activated protein kinase isoforms have already been implicated in B cell development, but the precise role of p38α in B cell differentiation is still largely unknown. Here we show that PC differentiation and antibody responses are severely impaired in mice with B cell-specific deletion of p38α, while B cell development and the GCB cell response are spared. By utilizing a Blimp1 reporter mouse model, we show that p38α-deficiency results in decreased BLIMP1 expression. p38α-driven BLIMP1 up-regulation is required for both TI and TD PCs differentiation. By combining CRISPR/Cas9 screening and other approaches, we identify TCF3, TCF4 and IRF4 as downstream effectors of p38α to control PC differentiation via Blimp1 transcription. This study thus identifies an important signalling pathway underpinning PC differentiation upstream of BLIMP1, and points to a highly specialized and non-redundant role for p38α among p38 isoforms.

Suggested Citation

  • Jianfeng Wu & Kang Yang & Shaowei Cai & Xiaohan Zhang & Lichen Hu & Fanjia Lin & Su-qin Wu & Changchun Xiao & Wen-Hsien Liu & Jiahuai Han, 2022. "A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34969-0
    DOI: 10.1038/s41467-022-34969-0
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