Location-directed functional dichotomy of CD11c in regulating B cell tolerance 3399
Bibliographic record
Abstract
Abstract Description Autoimmunity, aging and infection drive aberrant accrual of CD11c+ B cells. CD11c, or integrin ∝X (ITGAX), is a classic dendritic cell marker with dual identities of a complement receptor (CR4) and an integrin receptor. However, its functions on B cells remain elusive. Single nucleotide polymorphisms near ITGAX loci were identified as systemic lupus erythematosus (SLE) risk alleles. Additionally, patients with severe SLE demonstrated prominent accumulation of CD11c+ B cells. These findings underscore the need for functional characterization of B cell-intrinsic CD11c in autoimmunity. The debated functional and developmental heterogeneity within CD11c+ B cells suggest multifaceted roles of CD11c in maintaining B cell homeostasis. Using adoptive transfer and mixed bone marrow chimera models, we found that CD11c is critical for both central and peripheral tolerance maintenance. In the bone marrow, CD11c deficiency compromised mature B cell development yet supported spontaneous autoimmune germinal center development and autoantibody production. Splenic CD11c+ B cells demonstrated enhanced proliferation, while CD11c-deficient B cells failed to sustain in foreign naïve or autoimmune environments conferred by wild-type or 564Igi mice, respectively. These findings suggest that CD11c exerts functional dichotomy driven by tissue- and cell-specific expression. Understanding these location-specific mechanisms could uncover novel pathways regulating B cell tolerance and autoimmunity. Funding Sources Supported by NIH R01AR074105; R01AI130307; LRA: Lupus Mechanisms and Targets Award; CIHR Doctoral Foreign Study Award 202110DFD-475148-94277 Topic Categories Basic Autoimmunity (BA)
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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) | 0.002 | 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".