Increased Expression of the Inhibitory B-Cell Molecule CD22 on CD27+IgM+ B Cells Containing ABO-Antibody-Secreting Cells: A Role in Susceptibility to B-Cell Tolerance after ABO-Incompatible Infant Heart Transplantation?
Notice bibliographique
Résumé
Purpose: Immune immaturity allows ABO-incompatible heart transplantation (ABOi HTx) to be performed safely in infants and generally results in B-cell tolerance to donor ABO antigens. ABO antibodies are thought to arise in a T-independent (TI) manner; TI B-cell activation has been shown to be inhibited by the interaction of the inhibitory B-cell co-receptor CD22 with sialic acids on cells and tissues, leading to B-cell tolerance. It is unknown whether CD22 plays a role in regulating B-cell responses to ABO antigens in the transplant setting. Due to the generally reduced immune response to TI-antigens in early childhood, we hypothesized an enhanced role for CD22 during infancy compared to later in life. In this study we examined CD22 expression on various B-cell subsets. In addition, we performed functional assays to determine CD22 expression after B-cell stimulation and to assess the presence of ABO antigen-specific IgM antibody-secreting cells (ASC). Methods: We analyzed human splenocytes isolated from organ donors (n=41; ages 4 days - 74 years). Flow cytometric analysis was performed to quantify the expression levels of CD22, CD27, CD38, IgM and IgG on the surface of CD19+ B cells. CD27+IgM+ B cells and CD27−IgM+ B cells were isolated from human splenocytes (n=5) by automated magnetic activated cell sorting, labelled with Cell Proliferation Dye eFluor450 and stimulated with CpG plus IL-2, IL-10 and IL-15. After one week, CD22 expression was examined by flow cytometry and the frequency of ABO antigen-specific ASC detected by ELISPOT. Results: Significant differences were observed when comparing the median fluorescence intensity (MFI) of CD22 amongst various B-cell subsets (p< 0.0001; Kruskal Wallis test). Post testing using the Dunn's multiple comparison test revealed that CD27+IgM+ B cells had higher expression (p< 0.001) than other B-cell subsets. Furthermore, the MFI of CD22 on the CD27+IgM+ B cells was inversely correlated with age (p=0.001), with infant samples having the highest level of CD22, and expression decreasing with increasing age. After culture, down-regulated CD22 expression was observed in proliferating CD27+IgM+ B cells compared to non-proliferating cells. ELISPOT analysis showed that the vast majority of ABO antigen-specific ASC were derived from the CD27+IgM+ B-cell population. Conclusion: Based on previous studies showing the inhibitory role of CD22 on B-cell activation, our findings suggest that the increased expression of CD22 on the CD27+IgM+ B-cell subset, which includes precursors of ABO antigen-specific ASC, may cause these infant B cells to be more susceptible to down-regulation of B-cell signaling leading to subsequent inactivation. CD22 may therefore play an inhibitory role in immune responses to ABO antigens in the ABOi HTx setting. Studies are underway to determine the role of CD22 in B-cell signalling and regulation during infancy.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».