Polymeric IgA-secreting and mucosal homing pre-plasma cells in normal human peripheral blood
Bibliographic record
Abstract
Clear identification of recently activated mucosal B cells in human blood would greatly facilitate study of mucosal vaccines, immune response to infection and the ongoing mucosal IgA response. We examined blood lymphocytes from normal, healthy individuals to identify IgA-secreting pre-plasma cells' (PPC) functional and phenotypic relevance to mucosal antibody production, in the absence of infection, disease or recent vaccination. PPC are the most recently activated B lymphocytes in blood and are considered in transit between lymphoid tissue and effector tissues, where they terminally differentiate into plasma cells. We observed that all IgA-secreting PPC expressed surface IgA (sIgA) and intracellular IgA (icIgA) and secreted primarily polymeric IgA (pIgA), as determined by flow cytometry, ELISPOT and size exclusion chromatography. A large sub-population of PPC in blood expresses the mucosal chemokine receptor CCR10 and contains the largest fraction of sIgA and icIgA PPC that secrete pIgA. The majority of CCR10(+) PPC expresses high levels of Ki67, indicative of recently activated blasts. In contrast, most CCR10(-) PPC secrete IgG, but a small population secretes pIgA and stains for icIgA. The mucosal integrin alpha(4)beta(7) was detected on a subset of PPC, but this subset did not account for all CCR10(+) PPC or all PPC with sIgA expression. Our data clearly demonstrate that PPC defined by surface expression of CD19, CD27(hi), IgA and CCR10 secrete only pIgA and are the dominant mucosal PPC subset in human blood. These mucosal PPC can now be investigated routinely as indicators of recent human mucosal IgA 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 | 0.000 |
| 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".