WASP and Mst1 coregulate B-cell development and B-cell receptor signaling
Bibliographic record
Abstract
Mst1 is a serine/threonine kinase involved in cell survival, proliferation, apoptosis, and tumorigenesis. In mice, Mst1 regulates actin dynamics required for T-cell adhesion and migration, which correlate with thymic egress and entry into lymphatic tissue. The role of Mst1 in B cells and how it may control actin-dependent processes has not been well characterized. Wiskott-Aldrich syndrome protein (WASP) deficiency only moderately affects development and B-cell receptor (BCR) signaling, suggesting WASP likely associates with other molecules. We investigated whether Mst1 associates with WASP to regulate B-cell development and activation. Experimenting on Mst1/WASP double knockout (DKO) mice, we found a severe defect in the bone marrow B-cell development, and BCR signaling in the DKO mice was severely reduced. Even though WASP or Mst1 could influence the early B-cell activation, we found that the early activation events such as B-cell spreading, BCR clustering, and BCR signaling were much more impaired in the B cells from DKO mice. Furthermore, reciprocal regulation between Mst1 and WASP was observed in WASP and Mst1 KO mice, whereby the localization and function of phosphorylated WASP were affected in Mst1 KO mice. Most importantly, Mst1 inhibits the expression of WASP by decreasing the expression of WASP-interacting protein. Interestingly, we also found that WASP deficiency in patients and mice interferes with phosphorylated Mst1 localization and therefore function in B cells. Overall, our study provides a partner for WASP to regulate B-cell development and BCR signaling, as well as the reciprocal regulating molecular mechanism of one another.
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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".