Immunoglobulin VDJ repertoires reveal hallmarks of germinal centers in unique cell clusters isolated from zebrafish (Danio rerio) lymphoid tissues
Bibliographic record
Abstract
DNA mutagenesis during antibody affinity maturation has potentially oncogenic or autoimmune outcomes if not tightly controlled as it is in mammalian germinal centers. Cold blooded vertebrates lack germinal centers, yet have a functional Ig gene mutator enzyme, Aicda. In fish there are clusters of Aicda + cells encircled by pigmented ‘melano-macrophages’ and we test the hypothesis that these clusters are functionally analogous to germinal centers. Sequenced IgH VDJ repertoire libraries from individual isolated clusters showed evidence of B-cell clonal expansion and VDJ somatic hypermutation. Construction of Ig clonal lineage trees revealed that unlike surrounding lymphoid tissue, each cluster is dominated by a few B-cell VDJ clonotypes having hundreds of mutated variants. Recruitment of B-cells to the clusters appears to be ongoing, as there are additional Ig clones having smaller lineages. Finally, we show evidence for positive selection for replacement mutations in regions encoding the antigen contact loops, but not in the framework regions, consistent with functional antibody modification. Melano-macrophages appear to trap the Ag used for post-mutation B-cell selection, performing a role analogous to the follicular dendritic cells of mammalian germinal centers. These findings provide insights into the evolution of the affinity maturation process, the improvement of fish vaccines and possibly also the workings of atypical ectopic germinal centers generated in several human diseases.
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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 | 0.001 | 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".