| First Author | Di Pietro A | Year | 2022 |
| Journal | Nat Immunol | Volume | 23 |
| Issue | 1 | Pages | 86-98 |
| PubMed ID | 34845392 | Mgi Jnum | J:320901 |
| Mgi Id | MGI:6874441 | Doi | 10.1038/s41590-021-01077-y |
| Citation | Di Pietro A, et al. (2022) Targeting BMI-1 in B cells restores effective humoral immune responses and controls chronic viral infection. Nat Immunol 23(1):86-98 |
| abstractText | Ineffective antibody-mediated responses 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 BMI-1 in mice improves humoral responses to chronic lymphocytic choriomeningitis virus. BMI-1 was upregulated by germinal center B cells 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 chronic infection. |
