Systemic adjuvant inflammation rapidly reorganizes bone marrow B cell populations, and their niche, to shape B cell function and repertoire development (HEM1P.224)
Bibliographic record
Abstract
Abstract Maturing B cells migrate through the organized bone marrow parenchyma toward sinusoid vessels before entering circulation. Niche components rigorously control this process. Infecting mice with pathogens, or injecting inflammatory agents, is known to produce perturbations in B lymphopoiesis, however; it is poorly understood how the B cell niche responds to these challenges. Moreover, the impact on subsequent B cell function remains unknown. Here, we report that injection of Freund’s incomplete adjuvant in mice induced a large and rapid (within hours) mobilization of B cells to the bone marrow, mediated by increased sensitivity to the chemokine CXCL12. Notably, localization within the marrow is altered with all B cell subsets showing a reduced affinity for the sinusoids. Reorganization of B cell positioning occurred together with relevant modification of their supportive niche including increased expression of BAFF and MIF mRNA, expansion of DX5+Thy1loAPRIL+ basophils, and elevation of several important cytokines. This altered marrow milieu may have a role in shaping B cell fate, as we observed a decrease in lambda light chain usage in immature cells. Further, disruption of homing dynamics with a CXCR4 inhibitor attenuated the formation of IgM secreting cells. Together these results demonstrate an exquisite sensitivity of the marrow B cell compartment to peripheral inflammation and suggest that initial inflammatory signaling regulates subsequent B cell effector responses.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".