Systemic 4-1BB stimulation augments extrafollicular memory B cell formation and recall responses during Plasmodium infection 2954
Bibliographic record
Abstract
Abstract Description Germinal center (GC)-derived plasma cells (PC) and memory B cells (MBC) are pivotal for the effective clearance of Plasmodium and protection against reinfections. However, suboptimal humoral immune response, emergence of drug-resistant strains and difficulty of developing an efficacious vaccine have drawn keen interest towards host-directed immunotherapeutic approaches. Here, we demonstrate that exogenous stimulation of the costimulatory receptor 4-1BB, using a monoclonal antibody, enhances MBC response and improves protection from rechallenge, even though it delays the effector GC response. Functional and transcriptomic analysis demonstrate that MBCs from mice that received 4-1BB stimulation predominantly had an extrafollicular (EF) origin and showed superior recall and proliferative capacity. In addition, single cell ATAC sequencing revealed that these MBCs possessed a chromatin landscape that is permissive to transcription factors that govern PC differentiation. Importantly, our data also indicate that 3H3-driven protection is dependent on IFNγ and B cell-intrinsic T-BET-IL-9R signaling. In summary, our findings suggest that systemic 4-1BB stimulation in Plasmodium-infected mice promotes the generation of highly functional EF MBCs and signifies the potential of targeting the previously unappreciated IFNγ-T-BET-IL-9R axis to enhance humoral immune memory. Funding Sources Supported by 2024 AAI Careers in Immunology Fellowship; Schweppe Scholar Award (RFUMS); NIH : 1R01AI182217 (to R.V.) Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".