Nck proteins are recruited directly to the BCR and regulate PI3K signaling thereby shaping B cell immune responses (P1154)
Bibliographic record
Abstract
Abstract Binding of antigen to the B cell antigen receptor (BCR) triggers the activation of different kinases and the initiation of many signaling pathways required for mounting B-dependent immune responses. Scaffolding proteins, recruited downstream of the BCR, act as signal integrators through the recruitment of multiple signaling effectors. Nck is a family of scaffolding proteins best known for linking phosphotyrosine signals to cytoskeleton regulation but until now uncharacterized in the context of B lymphocytes. In our study, Nck was found to be directly recruited to the Igα tail of the BCR and to be important to regulate immune-receptor signaling. Through the generation of a novel Nck1 and Nck2 B cell conditional KO mouse model, we found these adaptors to be essential for mounting T-independent immune response and differentiate into extrafollicular plasma cells during T-dependent responses. The phenotype reported was shown to be due to defective PI3K signaling and Foxo1 downregulation in response to antigen challenge. Our work therefore provides the first compelling evidence for a critical role of Nck in BCR signaling, which is independent of its cytoskeleton regulation yet essential to mount B cell responses.
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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 | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".