Transplantation tolerance reduces the risk of infection, malignancy and cardiovascular disease caused by immunosupresive drugs. Indices of Tolerance revealed that tolerant kidney transplant recipients had an expansion of Bcells in peripheral blood. In parallel, a Bcell subset with regulatory properties has been described in humans as a transitional Bcell, characterised by high expression of CD38/24 and IL10 production. We set out to test the hypothesis that the expansion of this B cell subset was central in the process of spontaneous tolerance observed in these rare recipients and to test the ability of these cells to present alloantigens. Tolerant:functionally stable recipients without immunosuppressive drugs, stable:functionally stable recipients on standard immunosuppression, chronic rejector:immunosuppressed recipients that presented signs of chronic rejection and healthy controls samples were used in the study. Bcell subsets from patients were identified by flow cytometry with ΑCD20, ΑCD19, ΑCD27, ΑIgM, ΑIgG, ΑCD24 & ΑCD38. PBMCs were cultured 3 days alone, with CD40L and CpG, activation markers were measured by surface staining and IL10, IFN-Γ/TNF-Α were measured by flow and ELISA. Bcells were identified as CD20CD19 and memory B cells as CD27+. Within the CD27- non-memory Bcells we selected the IgDIgM population to study the non-class-switching Bcells and then we identified Transitional Bcells as CD24hiCD38hi. Within the CD27- population, transitional Bcells were more prevalent in tolerant patients (9,7%), in comparison with stable patients (2,4%), chronic rejectors (2,0%) and healthy controls (11,5%). Bcells from all groups of patients increased activation markers and TLR-9 after CD40L and CpG activation, respectively. Tolerant patients displayed a higher percentage of IL10+ Bcells in comparison with the rest of the groups in response to CD40L and CpG. CD40L interaction with Bcells occurs after encounter with activated Tcells. Only in this context Bcells from tolerant recipients were producing higher amounts of IL-10. This is a first step towards a firm link between an expansion of transitional Bcells and transplantation tolerance. Further studies are under way, to establish alloantigen specificity in this interaction.

« Back to 2013 American Transplant Congress