Kidney transplant recipients treated with belatacept exhibit increased naïve and transitional B cells

Abstract

Phase III clinical studies have shown that kidney transplant (KT) recipients treated with the costimulation blocker belatacept exhibited a better renal allograft function and lower donor-specific anti-HLA immunization when compared to recipients treated with calcineurin inhibitors (CNI). We analyzed B cell phenotype in KT recipients treated with belatacept and stable renal function (N = 13). Results were compared to those observed in stable patients treated with CNI (N = 12), or with chronic antibody-mediated rejection (N = 5). Both transcriptional profile and phenotypic characterization of peripheral B cells were performed by real-time polymerase chain reaction and flow cytometry, respectively. In belatacept group, the frequency and absolute number of transitional B cells as defined by both phenotypes: CD19(+) CD24(hi) CD38(hi) and CD19(+) IgD(hi) CD38(hi) CD27(-) , as well as naïve B cells were significantly higher compared with CNI group. B cell activating factor (BAFF) and BAFF receptor mRNA levels were significantly lower in belatacept group than in CNI group. These results show for the first time that belatacept influences B cell compartment by favoring the occurrence of transitional B cells with potential regulatory properties, as described in operational tolerant patients. This role may explain the lower alloimmunization rate observed in belatacept-treated patients.

Keywords: BAFF; BAFF-R; CTLA-4-Ig; belatacept; kidney transplantation; transitional B cells.