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

Yuichi Saito, Akihito Harada, Miho Ushijima, Kaori Tanaka, Ryota Higuchi, Akemi Baba, Daisuke Murakami, Stephen L. Nutt, Takashi Nakagawa, Yasuyuki Ohkawa () and Yoshihiro Baba ()
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Yuichi Saito: Kyushu University
Akihito Harada: Kyushu University
Miho Ushijima: Kyushu University
Kaori Tanaka: Kyushu University
Ryota Higuchi: Kyushu University
Akemi Baba: Kyushu University
Daisuke Murakami: Kyushu University
Stephen L. Nutt: The Walter and Eliza Hall Institute of Medical Research
Takashi Nakagawa: Kyushu University
Yasuyuki Ohkawa: Kyushu University
Yoshihiro Baba: Kyushu University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49375-x

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