The mutation <i>PTPN6</i>Ala455Thr causing pulmonary emphysema affects B cell populations and causes spontaneous pulmonary tertiary lymphoid tissue formation
Bibliographic record
Abstract
Abstract Rationale A new mutation causing severe pulmonary emphysema was recently discovered in a French-Canadian family. The mutation is located in the PTPN6 gene (PTPN6Ala455Thr) leading to a reduction in the activity of SHP-1, a phosphatase that regulates pathways associated to B cells. We aimed to characterize B cell abnormalities associated with aging in both humans and mice carrying this mutation. Methods Circulating B cell populations in humans carrying the PTPN6Ala455Thr mutation were analyzed by flow cytometry and immunoglobulin levels were measured in serum. In mice carrying the same mutation (Ptpn6Ala457Thr) aged up to 12 months, B cell populations were analyzed by flow cytometry and lung tissue histology performed. Mice were immunized with the T cell-independent antigen and NP-specific antibodies were measured in plasma. Results Human carriers of the PTPN6Ala455Thr mutation had reduced IgG1 and IgG4, and increased IgG3 levels as well as a lower ratio of naive B cells/ isotype switched memory B cells compared to controls. Aging Ptpn6Ala457Thr mice developed spontaneous pulmonary tertiary lymphoid tissues and exhibited higher proportion of B-1 cells, age-associated B cells and germinal center B cells along with lower B-2 cells in the lung and spleen. Ptpn6Ala457Thr mice had lower levels of NP-specific IgG1 antibodies compared to the wild-type group. Conclusion SHP-1 appears to affect aging of B cells as the PTPN6Ala455Thr mutation leads to changes in B cell populations associated with age, tertiary lymphoid tissue formation and an alteration of immunoglobulin levels. The link between B cell abnormalities, aging and emphysema requires further investigation. Funding:CIHR, FRQS CIHR, FRQS
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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 | 0.000 |
| 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 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".