Intrinsic defects in lymph node stromal cells underpin poor germinal center responses during aging
Denton, A. E.; Silva-Cayetano, A.; Dooley, J.; Hill, D. L.; Carr, E. J.; Robert, P.; Meyer-Hermann, M.; Liston, A.; Linterman, M. A.
Show abstract
The failure to generate enduring humoral immunity after vaccination is a hallmark of advancing age. This can be attributed to a reduction in the germinal center response, which generates long-lived antibody-secreting cells that provide protection against (re)infection. Despite intensive investigation into the effect of age on the lymphoid compartment, the primary cellular defect that causes impaired germinal centers in aging has not been identified. Herein we demonstrate that aging reduces the capacity of germinal center-associated stromal cells to respond to vaccination. Heterochronic parabiosis and mathematical modeling demonstrate that a poor stromal cell response limits the size of the germinal center. This study reveals that age-associated defects in stromal cells are a significant barrier to efficacious vaccine responses in older individuals.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Recruited macrophages that colonise the post-inflammatory peritoneal niche convert into functionally divergent resident cells 96%
- Metformin enhances anti-mycobacterial responses by educating immunometabolic circuits of CD8+ T cells 95%
- Senescent-like microglia limit remyelination through the senescence associated secretory phenotype 95%
Similar papers in this journal
- Fine-tuning spatial-temporal dynamics and surface receptor expression support plasma cell-intrinsic longevity 96%
- Early and Delayed STAT1-Dependent Responses Drive Local Trained Immunity of Macrophages in the Spleen 95%
- Microglia aging in the hippocampus advances through intermediate states that drive activation and cognitive decline 95%
Similar papers in this journal
- Cell-intrinsic functions of the transcription factor Bhlhe40 in activated B cells and T follicular helper cells restrain the germinal center reaction and prevent lymphomagenesis 95%
- Impaired immune response drives age-dependent severity of COVID-19 95%
- Epithelial antigen presentation controls commensal-specific intraepithelial T-cells in the gut 94%
Similar papers in this journal
- Functional impairment of "helpless" CD8+ memory T cells is transient and driven by prolonged but finite cognate antigen presentation 95%
- p16High immune cell - controlled disease tolerance as a broad defense and healthspan extending strategy 95%
- Diverse priming outcomes under conditions of very rare precursor B cells 95%
"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.