Congenital T-cell activation impairs transitional-to-follicular B-cell maturation in humans
Bibliographic record
Abstract
ABSTRACT: Patients with cytotoxic T-lymphocyte-associated protein 4 (CTLA4) deficiency 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 (FO) B-cell development in patients with CTLA4 deficiency, correlating with decreased CTLA4 function in regulatory T cells, increased CD40L levels in effector CD4+ T cells, and increased mammalian target of rapamycin complex 1 (mTORC1) signaling in transitional B cells (TrBs). Treatment of TrBs with CD40L was sufficient to induce mTORC1 signaling and inhibit FO B-cell maturation in vitro. Frequent cell-to-cell contacts between CD40L+ T cells and immunoglobulin D-positive CD27- B cells were observed in patient lymph nodes. FO B-cell maturation in patients with CTLA4 deficiency was partially rescued after CTLA4 replacement therapy in vivo. We conclude that functional regulatory T cells and the containment of excessive T-cell activation may be required for human TrBs to mature and attain metabolic quiescence at the FO B-cell stage.
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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 | 0.001 |
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 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".