RRC ID 69140
Author Luo Y, Zhang X, Chen R, Li R, Liu Y, Zhang J, Liu Q, Si M, Liu J, Wu B, Wang X, Wu S, Zhang Y, Zhang X, Guo D, He X, Pan T, Zhang H.
Title USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID.
Journal Signal Transduct Target Ther
Abstract Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants.
Volume 7(1)
Pages 7
Published 2022-1-4
DOI 10.1038/s41392-021-00858-z
PII 10.1038/s41392-021-00858-z
PMID 34983926
PMC PMC8724756
MeSH AIDS Vaccines / genetics AIDS Vaccines / immunology* Animals B-Cell Activating Factor / genetics B-Cell Activating Factor / immunology* COVID-19 Vaccines / genetics COVID-19 Vaccines / immunology* Cytidine Deaminase / genetics Cytidine Deaminase / immunology* HEK293 Cells HIV-1 / genetics HIV-1 / immunology* Humans Mice Mice, Knockout Nanoparticles* SARS-CoV-2 / genetics SARS-CoV-2 / immunology* Signal Transduction / genetics Signal Transduction / immunology* Ubiquitin Thiolesterase / genetics Ubiquitin Thiolesterase / immunology* Ubiquitination / immunology*
Mice RBRC00897