Phosphoinositide 3-kinase p110delta regulates natural antibody production, marginal zone and B-1 B cell function, and autoantibody responses (93.23)
Bibliographic record
Abstract
Abstract B-1 and marginal zone (MZ) B cells produce natural antibodies, make antibody responses to microbial pathogens, and contribute to autoimmunity. Although the delta isoform of the phosphoinositide 3-kinase p110 catalytic subunit (p110δ) is essential for development of these innate-like B cells, its role in mature B-1 and MZ B cells is not known. Using IC87114, a selective inhibitor of p110δ activity, we show that p110δ is important for B-1 and MZ B cell responses to anti-Ig antibodies, the Toll-like receptor (TLR) ligands LPS and CpG DNA, and the chemoattractants CXCL13 and sphingosine 1-phosphate. Moreover, we found that TLR-induced antibody responses by B-1 and MZ B cells, as well as the localization of MZ B cells in the spleen, depend on p110δ activity. Finally, we show that in vivo production of both protective and self-reactive natural antibodies requires p110δ and that p110δ inhibitors can reduce in vivo autoantibody responses. Thus targeting p110δ may be a novel approach for regulating innate-like B cells and treating antibody-mediated autoimmune diseases. Supported by a grant to M.R.G. from the Canadian Institutes of Health Research, by NIH grants to J.L.W., and a grant to J.L.W. from the Leducq Foundation.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".