Depletion of B cells induces remission of autoimmune hepatitis in mice through reduced antigen presentation and help to T cells
Bibliographic record
Abstract
UNLABELLED: Autoimmune hepatitis (AIH) is known as a T cell-mediated disease. However, AIH patients refractory to conventional treatment have been successfully treated with anti-CD20-mediated B-cell depletion. The aim of this project was to understand the immunological changes underlying the AIH remission caused by B-cell depletion in an experimental model of AIH. C57BL/6 AIH mice, xenoimmunized with DNA coding for human liver antigens, were treated with a single dose of depleting mouse anti-CD20 antibody at the peak of liver inflammation. Liver inflammation, alanine aminotransferase levels, chemokine (C-X-C) ligand 10 expression, and circulating B-cell, autoantibody, and total immunoglobulin G levels were monitored following depletion. T-cell and B-cell phenotype and function were characterized. Administration of a single dose of anti-CD20 resulted in a drastic reduction of liver inflammation accompanied by a significant reduction of alanine aminotransferase levels and of proinflammatory chemokine (C-X-C) ligand 10 expression. The treatment did not result in significant changes in total immunoglobulin G levels or autoantibodies. There were significantly more naive and less antigen-experienced CD4+ and CD8+ T cells, and T-cell proliferation was significantly reduced following anti-CD20 treatment. B cells served as antigen-presenting cells to CD4+ T cells. Anti-CD20 treatment also led to a profound reduction of T follicular helper cells. CONCLUSION: B cells play an active role in the pathogenesis of AIH in antigen presentation processes and the modulation of T-cell functions and influence the T follicular helper-cell population; this active role of B cells could explain the success of B-cell depletion for remission of AIH despite its classification as a T cell-mediated autoimmune liver disease.
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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 | 0.000 | 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) | 0.000 | 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".