E2F4 Plays a Critical Role in Early B-Cell Development.
Bibliographic record
Abstract
Abstract The E2Fs are important mediators of cell cycle control, DNA synthesis and apoptosis in many cell types. Recently E2F4 has been shown to play a role in hematopoietic cell growth and development (Rempel et al. Mol Cell, 6 p293, 2000). Here we report the effects of loss of E2F4 specifically on B-cell development. E2F4−/− mice have a partial block in early B-cell development prior to immunoglobulin gene rearrangement. The block is intrinsic to B-cell progenitors rather than secondary to micro-environmental effects since it occurs following transplant of E2F4−/− marrow into wild type recipients. Increases in apoptosis and abnormalities in cell cycle progression were found in B220+CD43+ B-cells of E2F4−/− mice indicating that E2F4 plays an important role in these processes in early B-cells. Expression of a variety of genes important in B-cell development including E2A, RAG, IL-7, EBF and Pax-5 were decreased in early E2F4−/− B-cells. In contrast, Id1 and Id2, regulators of a variety of genes critical to B-cell development, were relatively over-expressed in early E2F4−/− B-cells while Id3 was relatively under-expressed in these cells. E2F binding sites were identified in the Id2 and Id3 promoters and E2F4 was found to directly bind to these promoters in splenic B-cells. These findings suggest that E2F4 may also regulate early B-cell development by directly and indirectly modulating expression of the genes critical to B-cell differentiation. Together, these observations indicate that E2F4 is a critical mediator of early B-cell development via its effects on multiple pathways including those involved with apoptosis, cell cycle progression and differentiation. These findings also suggest that the E2Fs may serve to link cell survival and proliferation pathways to differentiation pathways in early B-cells and perhaps other cells aswell.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.004 | 0.002 |
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".