Targeting BMI-1 in B cells restores effective humoral immune responses and controls chronic viral infection
Journal Title
Nature Immunology
Publication Type
epub ahead of print
Abstract
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.
Publisher
NPG
WEHI Research Division(s)
Infectious Diseases And Immune Defence
PubMed ID
34845392
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-12-07 12:03:56
Last Modified: 2021-12-07 12:14:45
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