Allelic exclusion and differentiation by protein kinase C-mediated signals in immature thymocytes
Bibliographic record
Abstract
Pre-T cell receptor (preTCR)-derived signals mediate the transition of thymocytes from the CD4(-) CD8(-) double-negative (DN) to CD4(+) CD8(+) double-positive stage of T lymphocyte development. This progression, termed beta-selection, is limited to thymocytes that have generated a functional TCR-beta chain able to associate with pTalpha to form the preTCR complex. Formation of the preTCR complex not only induces differentiation, survival, and proliferation of DN thymocytes; it also inhibits further TCR-beta gene rearrangement through an ill-defined process known as allelic exclusion. The signaling pathways controlling this critical developmental checkpoint have not been characterized. Here we demonstrate that formation of the preTCR complex leads to the activation of protein kinase C (PKC), and that activation of PKC is necessary for the differentiation and expansion of DN thymocytes. Importantly, we also show that allelic exclusion at the TCR-beta gene loci is enforced by PKC-mediated signals. These results define PKC as a central mediator of both differentiation and allelic exclusion during thymocyte development.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".