Abstract 4140471: Deleting Tissue B-Cell Dynamics Prevents Angiotensin II-Induced Hypertension in Mice
Bibliographic record
Abstract
Background: Hypomorphic c-myb mice (with reduced B cells) manifest low baseline blood pressure [BP], increased 24-h urinary sodium and water excretion, and protection from DOCA salt-induced hypertension [HTN]. Here we study B cell dynamics and their role in angiotensin [Ang]-II-induced HTN using tissue flow cytometry [FC] and diphtheria toxin [DT]-induced B cell depletion in CD19-Cre/R26-iDTR mice. Methods&Results: To investigate B cell dynamics in HTN, wild-type [WT] C57BL/6J male mice aged 10-12 wk were implanted with either (a) 500 ng/kg/min x 28-d (low-dose) or (b) 1000 ng/kg/min x 28-d (high-dose) Ang-II, or (c) saline for FC of all B cell subsets in aorta, spleen, and bone marrow. CD19 + B cells in aorta increased 9.3-fold with low-dose (1.5±0.9E 2 vs. 1.4E 4 cells/aorta; N=1-4/group; p<0.01) and 8-fold with high-dose of Ang-II (1.5±0.9E 2 vs. 1.2±0.4E 4 ; N=2-4/group; p<0.01). In spleen, CD138 + plasma cells increased 3.4-fold with low-dose- (2.1±0.3E 5 vs. 7.2E 5 cells/spleen; N=1-4/group; p<0.001) but not with high-dose Ang-II (2.1±0.3E 5 vs. 1.3±0.1E 5 ; N=2-4/group; p=0.14). In bone marrow, plasma cells decreased 4-fold with low-dose (2.3±0.3E 6 vs. 0.59±0.6E 6 cells/bone marrow; N=2-4/group; p<0.05) but increased 2.2-fold with high-dose-Ang-II (2.3±0.3E 6 vs. 5.2±0.9E 6 cells/bone marrow; N=2-4/group; p<0.01). Then, 10-12-wk old male CD19-Cre/R26-iDTR mice and R26-iDTR controls were implanted with osmotic minipumps to deliver Ang-II (500 ng/kg/min) over 28-d. Intraperitoneal DT (25 ng/g) was injected weekly x 4 to both groups. Flow cytometry [FC] of blood and spleen at d-28 confirmed successful depletion of all B cell subsets in CD19-Cre/R26-iDTR but not R26-iDTR controls. BP measurements at d-28 showed attenuated HTN in B cell-depleted mice compared to non-depleted controls (94±15 vs. 134±12 mmHg; N=5/group; p<0.05). Metabolic studies revealed only non -B cell depleted mice to have increased 24-h Na + and urine excretion in response to Ang-II (N=4/group). Conclusion: CD19 + B cells infiltrate aorta during Ang-II-induced HTN. Ang-II levels regulate peripheral plasma cell homeostasis possibly through migration from/to or expansion within bone marrow and spleen. B cell depletion in the CD19-Cre/R26-iDTR model demonstrates the importance of B cell subtypes in the pathogenesis of Ang-II-induced HTN, suggesting a potential therapeutic strategy for HTN.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 0.004 |
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".