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Plasma cell differentiation is regulated by the expression of histone variant H3.3

Author

Listed:
  • Yuichi Saito

    (Kyushu University
    Kyushu University)

  • Akihito Harada

    (Kyushu University)

  • Miho Ushijima

    (Kyushu University)

  • Kaori Tanaka

    (Kyushu University)

  • Ryota Higuchi

    (Kyushu University
    Kyushu University)

  • Akemi Baba

    (Kyushu University)

  • Daisuke Murakami

    (Kyushu University)

  • Stephen L. Nutt

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Takashi Nakagawa

    (Kyushu University)

  • Yasuyuki Ohkawa

    (Kyushu University)

  • Yoshihiro Baba

    (Kyushu University)

Abstract

The differentiation of B cells into plasma cells is associated with substantial transcriptional and epigenetic remodeling. H3.3 histone variant marks active chromatin via replication-independent nucleosome assembly. However, its role in plasma cell development remains elusive. Herein, we show that during plasma cell differentiation, H3.3 is downregulated, and the deposition of H3.3 and chromatin accessibility are dynamically changed. Blockade of H3.3 downregulation by enforced H3.3 expression impairs plasma cell differentiation in an H3.3-specific sequence-dependent manner. Mechanistically, enforced H3.3 expression inhibits the upregulation of plasma cell-associated genes such as Irf4, Prdm1, and Xbp1 and maintains the expression of B cell-associated genes, Pax5, Bach2, and Bcl6. Concomitantly, sustained H3.3 expression prevents the structure of chromatin accessibility characteristic for plasma cells. Our findings suggest that appropriate H3.3 expression and deposition control plasma cell differentiation.

Suggested Citation

  • Yuichi Saito & Akihito Harada & Miho Ushijima & Kaori Tanaka & Ryota Higuchi & Akemi Baba & Daisuke Murakami & Stephen L. Nutt & Takashi Nakagawa & Yasuyuki Ohkawa & Yoshihiro Baba, 2024. "Plasma cell differentiation is regulated by the expression of histone variant H3.3," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49375-x
    DOI: 10.1038/s41467-024-49375-x
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