PubReading [69]- Targeting BMI-1 in B cells restores effective humoral immune responses and controls chronic viral infection - A. Di Pietro, K. Good-Jacobson et al

<p><strong>Ineffective antibody-mediated responses</strong> are a key characteristic of chronic viral infection. However, our understanding of the intrinsic mechanisms that drive this dysregulation are unclear. Here, we identify that targeting the epigenetic modifier <strong>BMI-1</strong> in mice improves humoral responses to chronic lymphocytic choriomeningitis virus. BMI-1 was upregulated by <strong>germinal center B cells</strong> in chronic viral infection, correlating with changes to the accessible chromatin landscape, compared to acute infection. B cell-intrinsic deletion of Bmi1 accelerated viral clearance, reduced splenomegaly and restored splenic architecture. Deletion of Bmi1 restored c-Myc expression in B cells, concomitant with improved quality of antibody and coupled with reduced antibody-secreting cell numbers. Specifically, BMI-1-deficiency induced antibody with increased neutralizing capacity and enhanced antibody-dependent effector function. Using a small molecule inhibitor to murine BMI-1, we could deplete antibody-secreting cells and prohibit detrimental immune complex formation in vivo. This study defines BMI-1 as a crucial immune modifier that controls antibody-mediated responses in <strong>chronic infection</strong>. - doi.org/10.1038/s41590-021-01077-y<strong> </strong>- 2021</p>