Increased negative selection impairs neonatal B cell repertoire but does not directly lead to generation of disease-associated IgM auto-antibodies
Bibliographic record
Abstract
To determine if increased negative B cell selection, due to lowered signaling threshold of responsiveness to a ligand as a result of SHP-1 deficiency, during ontogeny leads to the origin of disease-associated IgM auto-antibodies (AAbs), 47 V(H)J558+ VDJCmu rearrangements from SHP-1-deficient viable motheaten (me(v)/me(v)) and 24 J558+ VDJCmu rearrangements from normal me(v)/+ neonatal (<24 h post-birth) B cells were examined for their structural properties. None of the J558+ VDJCmu rearrangements from autoimmune-prone me(v)/me(v) had the characteristic CDR3H size restriction or arginine residues noted in disease-associated IgM AAbs. However, the MVAR2/10 genes are expressed at a high frequency in me(v)/me(v) (31.9%) as compared with me(v)/+ (16.7%), and pM11 gene expression is exclusively (14.9%) noted in me(v)/me(v) B cells. Clearly, there is a trend toward higher expression of pM11 genes (P-value < or = 0.09) in autoimmune-prone me(v)/me(v) strain. The CDR2H region of J558+ VDJCmu recombinations from me(v)/me(v) has increased hotspot triplets predisposing to mutations as compared with me(v)/+ (P-value < or = 0.01) mice. A higher DFL D-gene expression is noted in J558+ VDJCmu rearrangements from me(v)/me(v) (P-value < or = 0.1) in contrast to me(v)/+. The sophisticated logistic regression and odds ratio analysis of V-, D- and J-gene expressions in neonatal B cells from me(v)/me(v) and me(v)/+ mice demonstrates differential composition of the germ line IgM repertoire as a result of SHP-1 deficiency. These observations suggest that increased negative B cell selection during ontogeny impairs the developing IgM antibody repertoire but does not directly lead to generation of disease-associated IgM AAbs.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".