CD24 regulates the formation of ectosomes in B lymphocytes
Bibliographic record
Abstract
ABSTRACT CD24 is a glycophosphatidylinositol-linked protein that regulates B cell development. We previously reported that stimulation of CD24 on donor B cells promotes the transfer of functional receptors to recipient B cells via extracellular vesicles (EVs). However, the mechanisms regulating CD24-mediated formation of bioactive EVs are unknown. Using bioinformatics, we found a connection between CD24, and PI3K/AKT and mTOR. To determine if these pathways regulate EV release, we used flow cytometry to follow the transfer of EVs carrying lipid- associated GFP and surface IgM from donor to recipient B cells. Using chemical and genetic inhibition, we found that a PI3K/mTORC2/ROCK/actin pathway regulates bioactive EV formation via activation of acid sphingomyelinase (aSMase) upstream of PI3K. Using single EV analysis, we found that CD24 regulates the formation of the subset of bioactive EVs that are taken up by recipient cells and not total EVs. Interestingly, we also found that ROCK and aSMase modulate ectosome but not exosome formation, when CD24 is stimulated. Lastly, through live cell imaging, we found that PI3K and ROCK are required for inducing membrane dynamics associated with EV formation. These data suggest that this pathway regulates bioactive EV release that, in turn, could regulate B cell development. Graphical TOC/Abstract Bioinformatics analysis followed by genetic and chemical experiments revealed that a novel pathway regulates EV release downstream of CD24; namely aSMase/PI3K/mTORC2/ROCK/actin. Single EV analysis suggests that the EVs are ectosomes and that CD24 regulates packaging of cargo to create bioactive vesicles rather than regulating total EV release. Live cell imaging shows that CD24 regulates membrane dynamics.
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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 | 0.001 |
| 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".