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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".