Identification of a novel subset of activation induced deaminase (AID)-dependent B-1 cells that mediate Initiation of Contact Sensitivity (37.10)
Bibliographic record
Abstract
Abstract Contact sensitivity (CS) to haptens is related to delayed type hypersensitivity (DTH) and is a well characterized prototype of T cell mediated inflammation. CS is additionally dependent on a parallel immune pathway. In response to sensitization, a population of B-1 cells produces antigen-specific IgM which mediates a rapid inflammatory response to hapten re-exposure. Interference with this pathway prevents the full development of the classic delayed response and is therefore termed the “CS-Initiation” pathway. The identity of the B-1 cell subset responsible for CS-Initiation is not known. Here, we show that CS-Initiation is dependent on activation induced deaminase (AID), an enzyme central to the process of somatic hypermutation (SHM). Using adoptive transfer experiments, we demonstrate that the defect is specific to B-1 cells as transfer of wild type B-1 cells reconstitutes CS-Initiation in deficient recipients. We went on to identify and characterize a unique subpopulation of B-1 cells in the spleens of sensitized mice that possess initiation activity. Detailed analysis of B cell receptor genes isolated from these cells revealed evidence of AID-mediated SHM. The sensitivity of CS-Initiation to very low amounts of hapten and the dependence on AID suggests that these cells are selected to generate antibodies capable of mediating CS-Initiation. This work funded by the Canadian Institutes of Health Research, the American Academy of Allergy, Asthma and Immunology and the National Institutes of Health.
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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 | 0.003 | 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 | 0.000 | 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".