Ptpn2 limits plasma cell fate and antiviral immunity by integrating B cell receptor and IFN-γ signals in B cells

B cell activation and subsequent plasma cell differentiation are two crucial processes in the establishment of long-term immunity. Understanding the signaling pathways that regulate B cell function and terminal differentiation is crucial to human health. Ptpn2 is a protein tyrosine phosphatase whose role in limiting immune cell activation is well chatacterized. However, it is not known whether Ptpn2 plays a cell-intrinsic role in regulating B cell development and activation. Using a Ptpn2 B-cell-specific knockout mouse model we have discovered a novel role for Ptpn2 in negatively regulating both BCR and IFN-gamma signaling in B cells. As a result, the absence of Ptpn2 leads to the enhanced terminal differentiation of B cells into plasma cells. Consequently, mice lacking Ptpn2 in B cells present improved antibody responses against viral infections, such as Influenza A virus. Overall, our results reveal a novel role for Ptpn2 in B cell activation, highlighting its potential as a therapeutic target to optimize vaccine responses and enhance immunity against infectious diseases.