Interaction of TAPP adapter proteins with phosphatidylinositol (3,4)-bisphosphate regulates B cell activation and autoantibody production (159.5)
Bibliographic record
Abstract
Abstract Activation of PI3-kinase enzymes through the BCR is essential for B cell development and function. Active PI3Ks generate D3 phosphoinositide PI(3,4)P2 that bind to signaling molecules such as TAPP (Tandem PH domain containing protein) adaptor via their C terminal PH domain. This interaction leads to translocation of TAPPs to the plasma membrane. However, the role of TAPP adaptors in regulating PI3K signaling in B cell is not completely understood. We have performed studies on TAPP mutant mice, where a mutation was introduced to the C terminal domain of both TAPP1 and TAPP2 to determine the effect of uncoupling TAPPs from PI(3,4)P2. The studies showed an enhanced B cell activation and elevated serum antibody levels in these mice, suggesting an inhibitory role associated with TAPPs in B cells. To test whether the aberrant responses observed in B cells leads to autoimmunity in these animals, we analyzed their serum and observed a progressive increase in anti-dsDNA antibodies in the aging cohort. This along with other observed characteristics such as the presence of anti-nuclear antibodies within the serum, progressive development of lymphopenia and glomerulonephritis in aged mice is reminiscent of lupus. We are currently working to define the cellular interactions involved in this autoimmune phenotype and the signaling mechanism associated with the inhibitory role of TAPPs.
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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) | 0.000 | 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".