Systemic 4-1BB stimulation augments extrafollicular memory B cell formation and recall responses during Plasmodium infection

T-dependent germinal center (GC) output, comprising plasma cells and memory B cells (MBCs), is crucial for clearance of Plasmodium infection and protection against reinfection. In this study, we examine the effect of an agonistic antibody targeting 4-1BB (CD137) during experimental malaria. We show that exogenous 4-1BB stimulation, despite delaying the effector GC response, surprisingly enhances humoral memory recall and protection from reinfection. Single-cell RNA and assay for transposase-accessible chromatin (ATAC) sequencing of MBCs from mice receiving 4-1BB stimulation reveal populations with distinct transcriptional signatures and a chromatin landscape indicative of superior recall and proliferative potential. Importantly, our results indicate that the effects of 4-1BB stimulation are dependent on interleukin (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.

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Publication Details

Journal
Cell Reports
Published
2025-04-01
DOI
https://doi.org/10.1016/j.celrep.2025.115528
Citations
2
Primary Topic
Neuroinflammation and Neurodegeneration Mechanisms
Type
article
Field-Weighted Citation Impact
1.68

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article

Systemic 4-1BB stimulation augments extrafollicular memory B cell formation and recall responses during Plasmodium infection

Akshaya Ramachandran, Scott E. Lindner, Taylor A. Lyons, Anthony Cannon et al.
2 citations
Cell Reports
Neuroinflammation and Neurodegeneration Mechanisms
1.68
article

Systemic 4-1BB stimulation augments extrafollicular memory B cell formation and recall responses during Plasmodium infection

Akshaya Ramachandran, Scott E. Lindner, Taylor A. Lyons, Anthony Cannon, Mark H. Kaplan, Rahul Vijay, Allen M. Minns, Tania H. Watts, Alexandria J. Sturtz, Lijo John, Justin P. Whalley, Carolina Calôba
article en
2 citations

Abstract

T-dependent germinal center (GC) output, comprising plasma cells and memory B cells (MBCs), is crucial for clearance of Plasmodium infection and protection against reinfection. In this study, we examine the effect of an agonistic antibody targeting 4-1BB (CD137) during experimental malaria. We show that exogenous 4-1BB stimulation, despite delaying the effector GC response, surprisingly enhances humoral memory recall and protection from reinfection. Single-cell RNA and assay for transposase-accessible chromatin (ATAC) sequencing of MBCs from mice receiving 4-1BB stimulation reveal populations with distinct transcriptional signatures and a chromatin landscape indicative of superior recall and proliferative potential. Importantly, our results indicate that the effects of 4-1BB stimulation are dependent on interleukin (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.

Cell ReportsVol. 44(4)
Pennsylvania State University (US), University of Toronto (CA), Rosalind Franklin University of Medicine and Science (US), Washington University in St. Louis (US), Kerala Veterinary and Animal Sciences University (IN), Kerala University of Health Sciences (IN), Indiana University School of Medicine, Indiana University – Purdue University Indianapolis (US)
American Association of Immunologists, Rush University, Rosalind Franklin University of Medicine and Science, National Institutes of Health
Zero hunger
Openalex Percentile: Top 17%
Neuroinflammation and Neurodegeneration Mechanisms
1.68
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