Antibody Response to Non-Self Blood Group A-Antigen depends on CD4 T Cells, Forigen Protein and CD22 Interaction
Bibliographic record
Abstract
Background ABO-incompatible heart transplantation (ABOi-HTx) is safe during infancy and allows increased donor access. B-cell tolerance develops to donor A/B-antigen(s) (Ag) after ABOi-HTx by mechanisms remaining unclear. We developed transgenic mice (A-Tg) constitutively expressing human A-Ag on vascular endothelium and erythrocytes (RBC) to study anti-A antibody responses. CD22 participates in B-cell tolerance and we found that B cells express high-levels of CD22 in human B cells, decreasing with age. Here we used a mouse model to study the anti-A response in the context of MHC syngeneic, allogeneic and xenogeneic stimulation, and the impact of CD22 expression. Methods Part I: Adult wild-type (WT) C57BL/6 (B6/H-2b), BALB/c (BALB/H-2d), C3H/He (C3H/H-2k), or CD22-deficient B6 (CD22KO) mice received intraperitoneal injections of B6 or BALB A-Tg blood cells or human-RBC membranes (100ul/10%v/v) from blood group-A (hu-A) or O (hu-O); or A-incompatible heart allografts. Serum anti-A Ab was measured by hemagglutination and ELISA (IgG and IgM); graft survival was assessed by palpation. Part II: a) To assess requirement of foreign protein to stimulate anti-A, hu-O RBC/syngeneic A-Tg cells or allogeneic A-Tg blood were co-injected in WT mice; b) to assess T cell dependence of anti-A response, CD4+ T cells were depleted from WT B6 mice before hu-A RBC injection. Part III: To assess the role of CD22, A-Tg or hu-A-RBC, were injected into CD22KO mice with or without CD4+ T-cell depletion. Results Part I: Exposure to allogeneic A-Tg blood cells/heart graft or xenogeneic hu-RBC induced anti-A production (Table), whereas syngeneic A-Tg blood cells did not. Part II: a) mixture of syngeneic A-Tg/hu-O RBC did not induce anti-A; b) after CD4+ T-cell depletion, hu A-RBC failed to elicit anti-A. Part III: Hu A-RBC induced a very high anti-A in CD22KO mice compared to WT B6. In contrast to WT B6 mice, anti-A Ab was elicited in CD22KO mice following injection with A-Tg blood cells or hu A-RBC with CD4+ T cell depletion.Conclusions Our results show that in WT mice, anti-A antibody production depends not only on exposure to A-antigen but also co-engagement with foreign protein and a requirement for CD4+ cells; consistent with a T-dependent anti-A response. Conversely, in CD22KO mice there was no requirement for foreign protein or CD4+ cells to elicit an anti-A antibody response; consistent with a T-independent anti-A response. These findings suggest an important role for the regulatory CD22 receptor in the B cell response to ABH antigens.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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) | 0.004 | 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".