THE ROLE OF B CELLS IN ANTI-CD45RB INDUCED TRANSPLANTATION TOLERANCE.
Bibliographic record
Abstract
P951 Aims: We have recently demonstrated that anti-CD45RB induced transplantation tolerance is unique in that it is dependent on the presence of host B cells. In this study, we aimed to determine the underlying mechanisms of B cell participation in this model by focusing on their potential contribution to antibody production and/or antigen presentation. Methods: To determine the role of antibody secretion by B cells in prolonging cardiac allograft survival, B6-HEL-transgenic mice, where B cells are engineered to be specific for the Hen Egg Lysozyme (HEL) antigen and therefore do not secrete antibody in response to any other alloantigen, were transplanted with C3H mice cardiac grafts, and then treated with anti-CD45RB antibody (100μg ip. on days 0,1,3,5 and 7). To determine the antigen presentation role of B cells, we adoptively transferred B cells from MHC Class II transactivator deficient mice (CIITA) into B cell deficient mice (μMT) and used them as recipients of C3H hearts. Transplanted mice also received our standard 5 dose of anti-CD45RB treatment. Results: In wide-type B6 mice C3H cardiac allografts (N=9) were rejected acutely (MST=8.2±1.9 days). In contrast, in B6 mice treated with anti-CD45RB the majority (66%) of grafts (N=9) survived > 100 days (MST >83±30 days). However, the same anti-CD45RB protocol administered to B6-HEL mice resulted in rapid rejected C3H grafts (MST = 12.3±3.0 days; n = 8); In contrast, all the B cell deficient mice reconstituted with CIITA B cells accepted cardiac allografts indefinitely (MST >100 days; n=9). Conclusions: Our preliminary results indicate either the antibody secretion by B cells or the B cell receptor mediated uptake of specific alloantigen is required for the B cells to induce cardiac allograft tolerance in the setting of anti-CD45RB. On the other hand, the APC function of B cells via MHC class II does not seem to be critical for the successful induction of transplantation tolerance induced by CD45RB. These results help define a novel pathway of B cell dependent T cell tolerance.
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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) | 0.001 | 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".