The histone H2B ubiquitination regulator Wac is essential for plasma cell differentiation

Naïve 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.