| Abstract |
Nucleolar protein 16 (NOP16) has been increasingly implicated in promoting tumorigenesis and was recently identified as a novel epigenetic regulator. However, its physiological role in nonmalignant cells remains poorly understood. Although NOP16 is ubiquitously expressed across various tissues and cell types, we found it to be preferentially upregulated in activated B cells, whereas its level in light zone germinal center (GC) B cells within human tonsils and vaccinated mice-derived spleen were higher than in dark zone levels. In 2 independent murine B cell lines, stimulation with TGF-β, IL-4, and CD40 ligand, to induce class switch recombination (CSR) from IgM to IgA, led to a downregulation of NOP16 and a concomitant upregulation of activation-induced cytidine deaminase (AID). We found that TGF-β mediates the downregulation of NOP16. Moreover, RNA-seq analysis revealed that knockdown of NOP16 markedly increased AID expression in B cells. Interestingly, knockdown of NOP16 enhanced class switching to IgA by upregulating AID induction in both murine B cell lines. NOP16 knockdown did not affect class switching to IgG2b or IgG3, suggesting isotype-specific regulation. These findings identify NOP16 as a previously unrecognized modulator of CSR, highlighting its physiological relevance in adaptive immunity and extending its functional significance beyond cancer biology.
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