IL-17 promotes germinal center response and AID-regulated pathogenic autoantibody production in autoimmune BXD2 mice (130.21)
Bibliographic record
Abstract
Abstract We have found dramatically elevated levels of activation-induced cytidine deaminase (AID) in the B cells of generalized autoimmune BXD2 mice that develop spontaneous erosive arthritis and glomerulonepheritis. Pathogenic autoantibodies cloned from these mice exhibit extensive somatic hypermutation and the majority of them have undergone class-switch recombination, suggesting that AID activity plays an important role in the production of pathogenic autoantibodies. Sera from BXD2 mice exhibited significantly elevated IL-17, but not IFN-γ or IL-4, compared to B6 mice. FACS analysis indicates that CD4 T cells in BXD2 mice are preferentially polarized to Th17 cells and these cells also express the early activation marker, CD69, in vivo in BXD2 mice. The B cells from BXD2 mice express high levels of IL-17 receptor (IL-17R) and immunohistochemistry staining shows that B cells are in close contact with the IL-17+ cells in the spleen. Administration of AdIL-17 to 1-mo-old B6 and BXD2 mice induced the expression of AID, promoted development of GCs, and enhanced the sera titers of antibodies. In contrast, administration of AdIL-17R:Fc to 10-mo-old BXD2 mice suppressed the expression of AID, down-modulated the percentage of PNA+Fas+ GC B cells, and suppressed the sera titers of antibodies. Our results provided a unique pathogenic function of IL-17 in that it positions IL-17 as a critical cytokine that regulates GC B cell response and the production of pathogenic autoantibodies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".