A novel mechanism regulating anti-viral humoral response: interplay between IL-21, LAPC and TFH in anti-IAV humoral response. (P6174)
Bibliographic record
Abstract
Abstract The humoral immune response to most respiratory virus infections plays a prominent role in virus clearance and is essential for resistance to reinfection. T follicular helper (TFH) cells are believed to support the development both of a potent primary antibody response and of the germinal center response critical for memory B cell development. Using a model of primary murine influenza A virus (IAV) infection, we demonstrate that a novel APC, the LAPC (Late-activator APC), promotes the TFH response in the draining LNs (dLNs) of the IAV-infected lungs. LAPCs migrate from the infected lungs to the dLN "late," i.e., 6 d after infection, which is concomitant with TFH differentiation. LAPC migration is CXCR3-CXCL9-dependent, and LAPC triggering of TFH cell development requires ICOS-ICOSL-dependent signaling. In IAV infection, the host immune system control this LAPC-mediated TFH differentiation via IL-21.We have demonstrated that IL-21, a well known TFH differentiation inducing factor, produced by NK T-cells in the dLN acts on lymph node resident T cells to stimulate TNF-α release by the T-cells. TNF-α in turn stimulates dLN resident dendritic cells to secrete CXCL9, a potent chemotactic stimulus for migration of CXCR3 expressing lung resident LAPC into the dLN. It is then the migrant LAPC which acts to modulate TFH differentiation during respiratory viral infection. Our results reveal a novel and previously unsuspected mechanism for regulating anti-viral TFH and humoral responses.
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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 | 0.000 |
| 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".