CD19+,CD27+, IgM+ B Cells of Patients with Persistent Polyclonal B Cell (PPBL) Proliferate in a Low Intensity CD40-CD154 Interaction and Show Evidence of Immunoglobulin Isotype Switching
Notice bibliographique
Résumé
Abstract Persistent polyclonal B cell lymphocytosis (PPBL) is a rare disorder characterized by an expansion of memory B cells CD19+, CD27+, IgM+. PPBL occurs mainly in female, is associated with HLA DR7, an increased level of serum IgM and the lymphocytes frequently show a bi-nucleated morphology. The patients have in most cases smoking habits and the clinical evolution is usually benign but we have previously described one case of lymphoma 19 years after a diagnosis of PPBL. Although the pathophysiology remains unknown, a familial occurrence is at the basis of this disorder suggesting a genetic defect. Moreover, multiple bcl-2\Ig gene rearrangements are present in all patients and an extra isochromosome 3 (i3)(q10) is frequently shown in the B cell population. The binding of CD40 to CD154 expressed on activated T cells plays a central role in B cell activation, proliferation and Ig isotype switching. We have previously shown that PPBL B lymphocytes were unable to respond to the proliferative signal delivered in vitro by CD40 in the CD40-CD154 system, indicating a possible defect in the CD40 pathway although CD40 expression, sequencing and tyrosine phosphorylation appeared normal. However, it has been shown recently that a reduced intensity of CD40-CD154 interaction in the presence of IL-2, IL-4 and IL-10 results in the proliferation, expansion and immunoglobulin secretion of normal memory CD19+,CD27+, IgM+ B cells. PPBL B lymphocytes sharing the same phenotype as normal memory B cells, we design a study to investigate the response of B lymphocytes from patient with PPBL in culture in high and low CD154 interaction. Proliferation and flow cytometry analysis of B lymphocytes from 6 patients with PPBL were closely monitored through a 14 day culture period and the Ig secretion was determined by Elisa. Our results show that a low intensity CD40- CD154 interaction in the presence of IL-2, IL-4 and IL-10 induces proliferation of the CD19+,CD27+,IgM+ PPBL population 6 to 20 times higher compared to high CD154 interaction. Interestingly, the CD19+, IgG+ cell population that constitutes less than 5% of the cell population at the beginning of the culture, increased over 25% on day 14. As for normal controls, we observed the emergence of a CD19+,CD27− cell population and the disappearance of surface IgD. Culture of B cells from patients with PPBL resulted in high Ig secretion. Moreover on day 14, Ig isotype analysis showed higher IgG levels compared to IgM. We conclude that PPBL B lymphocytes could proliferate in the CD40- CD154 system under proper condition and that proliferation also results in IgM and IgG secretion indicating an adequate CD40 signalling pathway. Moreover, this report provides the first evidence of in vitro Ig isotype switching of CD19+,CD27+,IgM+ B lymphocytes from PPBL. These results also suggest a possible defect in the interaction with T cells as observed in the hyper-IgM syndrome or alternatively, other cells from the microenvironment.
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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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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 | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 ».