Congenital T cell activation impairs transitional to follicular B cell maturation in humans
Bibliographic record
Abstract
Abstract CTLA4-deficient patients exhibit profound humoral immune dysfunction, yet the basis for the B cell defect is not known. We observed a marked reduction in transitional to follicular B cell development in CTLA4-deficient patients, correlating with decreased CTLA4 function in regulatory T cells and increased mTORC1 signaling in transitional B cells. Treatment of transitional B cells with CD40L was sufficient to induce mTORC1 signaling and inhibit follicular B cell maturation in vitro . Frequent cell-cell contacts between CD40L + T cells and naïve IgD + CD27 − B cells were observed in patient lymph nodes. Follicular B cell maturation in CTLA-deficient patients was partially rescued following CTLA4 replacement therapy in vivo . We conclude that functional regulatory T cells and the containment of excessive T cell activation are required for follicular B cells to mature and attain metabolic quiescence and thus acquire a state of immunological self-tolerance. One Sentence Summary Congenital T cell activation in CTLA4-deficient patients impairs transitional to follicular B cell maturation and can be rescued by CTLA4 replacement therapy in vivo .
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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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".