Exogenous 4-1BB co-stimulation enhances memory B cell response during malaria.
Caloba, C.; Sturtz, A.; Ramachandran, A.; John, L.; Malkina, K.; Minns, A. M.; Lindner, S. E.; Vijay, R.
Show abstract
T-dependent germinal center (GC) output, comprising plasma cells (PC) and memory B cells (MBC), is crucial for the clearance of Plasmodium infection and protection against reinfection. In this study, we examined the effect of an agonistic antibody targeting 4-1BB (CD137), a member of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF), during experimental malaria. Here we show that exogenous 4-1BB stimulation, despite delaying the effector GC response, surprisingly enhanced humoral memory recall and protection from reinfection. Single cell RNA and ATAC sequencing of MBCs from mice that received 4-1BB stimulation revealed distinct populations with transcriptional and epigenetic signatures indicative of superior recall and proliferative potential. Importantly, our results indicate that the effects of 4-1BB stimulation are dependent on IL-9R signaling in B cells but independent of parasite load during primary infection. Our study proposes an immunomodulatory approach to enhance the quality of the MBC pool, providing superior protection during infection and vaccination, particularly in the context of malaria.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- CD4+ T cells display a spectrum of recall dynamics during re-infection with malaria parasites. 98%
- Inducible nitric oxide synthase (iNOS) is necessary for GBP-mediated T. gondii restriction in murine macrophages via vacuole nitration and intravacuolar network collapse 97%
- T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling 96%
Similar papers in this journal
- The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development 96%
- A negative feedback loop mediated by the NR4A family of nuclear hormone receptors restrains expansion of B cells that receive signal one in the absence of signal two 96%
- A novel mouse model based on intersectional genetics enables unambiguous in vivo discrimination between plasmacytoid and other dendritic cells and their comparative characterization 96%
Similar papers in this journal
- The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+ CD8+ effector state and its deletion improves checkpoint blockade 95%
- Temporal associations of B and T cell immunity with robust vaccine responsiveness in a 16-week interval BNT162b2 regimen 95%
- Optimal CXCR5 Expression during Tfh Maturation Involves the Bhlhe40-Pou2af1 Axis 95%
Similar papers in this journal
- IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections 96%
- TET2 regulates early and late transitions in exhausted CD8+ T-cell differentiation and limits CAR T-cell function 96%
- Deconvoluting TCR-dependent & -independent activation is vital for reliable Ag-specific CD4+ T cell characterization by AIM assay 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.