Regulation of B cell responses in allergy by histamine receptors
Bibliographic record
Abstract
Abstract Histamine is a bioactive amine stored in mast cells and basophils and released upon antigen-specific IgE-dependent activation, mediating responses during allergic reactivity, including vasodilation, smooth muscle constriction and inflammatory cell recruitment. These are regulated through four receptors (H1R-H4R) that are differentially expressed on various cell types. Despite this, increasing evidence suggests that histamine can be produced during the priming phase of allergen responses, with H4R on dendritic cells being important for initiating Type 2 immunity. Here, we sought to determine the roles of these receptors in supporting antigen-specific B cell responses. Interestingly, our data demonstrates that both murine and human B cells only expressed H1R and H2R; these also showed differential expression levels on specific B cell subsets and upon activation. Using an Ovalbumin-alum (OVA-alum) model of allergic immunization, mice lacking H2R produced significantly lower levels of OVA-IgE, whereas mice lacking H1R were unaffected. Surprisingly, absence of both H1R and H2R (H1R/H2R DKO) exhibited undetectable levels of OVA-IgE. This was not due to T cell-intrinsic influences since restimulation of splenocytes from immunized H1R/H2R DKO mice showed that Th2 cytokine production was unaltered compared to WT. Instead, in vitro stimulation of B220+ B cells by αCD40 and IL-4 yielded significantly lower IgE production from H1R/H2R DKO mice than WT and defines a key requirement for these receptors in permitting B cells from generating IgE antibodies. Our data establishes a novel requirement for histamine, a molecule typically considered in regulating allergic responses, in supporting the generation of allergic sensitivity.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 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".