PI3K-dependent reprogramming of hexokinase isoforms controls glucose metabolism and functional responses of B lymphocytes
Bibliographic record
Abstract
<h2>Summary</h2> B lymphocyte activation triggers metabolic reprogramming essential for B cell differentiation and mounting a healthy immune response. Here, we investigate the regulation and function of glucose-phosphorylating enzyme hexokinase 2 (HK2) in B cells. We report that both activation-dependent expression and mitochondrial localization of HK2 are regulated by the phosphatidylinositol 3-kinase (PI3K) signaling pathway. B cell-specific deletion of HK2 in mice caused mild perturbations in B cell development. HK2-deficient B cells show impaired functional responses <i>in vitro</i> and adapt to become less dependent on glucose and more dependent on glutamine. HK2 deficiency impairs glycolysis, alters metabolite profiles, and alters flux of labeled glucose carbons into downstream pathways. Upon immunization, HK2-deficient mice exhibit impaired germinal center, plasmablast, and antibody responses. HK2 expression in primary human chronic lymphocytic leukemia (CLL) cells was associated with recent proliferation and could be reduced by PI3K inhibition. Our study implicates PI3K-dependent modulation of HK2 in B cell metabolic reprogramming.
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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 | 0.001 | 0.001 |
| 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".