The histone H2B ubiquitination regulator Wac is essential for plasma cell differentiation
- 23 May 2023
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 597 (13), 1748-1760
- https://doi.org/10.1002/1873-3468.14633
Abstract
Naive B cells become activated and differentiate into antibody-secreting plasma cells (PCs) when encountering antigens. Here, we reveal that the WW domain-containing adapter protein with coiled-coil (Wac), which is important for histone H2B ubiquitination (ubH2B), is essential for PC differentiation. We demonstrate that B cell-specific Wac knockout mice have severely compromised T cell-dependent and -independent antibody responses. PC differentiation is drastically compromised despite undisturbed germinal center B cell response in the mutant mice. We also observe a significant reduction in global ubH2B in Wac-deficient B cells, which is correlated with downregulated expression of some genes critical for cell metabolism. Thus, our findings demonstrate an essential role of Wac-mediated ubH2B in PC differentiation and shed light on the epigenetic mechanisms underlying this process.Funding Information
- National Natural Science Foundation of China (32170882)
- Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20190809161807432, JCYJ20220530115212028)
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