Belatacept does not inhibit plasmablast formation supported by follicular T helper cells, but favors the development of transitional regulatory B cells in kidney transplant patients

G.N. de Graav, D.A. Hesselink, M. Dieterich, R. Kraaijeveld, W. Weimar, C.C. Baan

Chair(s): dr. Hennie G. Otten, medisch immunoloog, UMC Utrecht & dr. Laura B. Bungener, medisch immunoloog, UMC Groningen

Thursday 10 march 2016

9:50 - 10:00h at Zaal 1 & 2

Categories: Parallelsessie (basaal)

Parallel session: Parallelsessie VII - Basaal immunologie

The costimulatory inhibitor belatacept effectively blocks T-B cell interaction in animal transplant models. We studied the functional follicular T helper cells (TFH)-B cell interaction in belatacept-treated patients to determine the effects of this drug in human kidney transplantation. The presence of CXCR5+PD-1+CD4+ TFH cells, CD19+CD27+CD38++ plasmablasts and CD19+CD24++CD38++ transitional B cells was assessed in the circulation of belatacept-treated and tacrolimus-treated patients (n=40), and in vitro after donor antigen re-stimulation in the presence and absence of therapeutic concentrations of belatacept (10 µg/mL) or tacrolimus (10 ng/mL). PBMCs were obtained 3 months after transplantation or during an acute rejection episode (before additional therapy was given). The proportion of TFH-cells and their allogeneic IL-2 and IL-21 production were measured as well as the differentiation of B cells into TNFα-producing effector plasmablasts and transitional IL-10+ regulatory B cells (Bregs). In belatacept-treated patients, the frequency of circulating TFH cells was low before transplantation (0.6 cells/µL), and did not change after. The number of circulating plasmablasts and transitional B cells dropped under belatacept treatment (from 0.3 to 0.2 cells/µL, p=0.006, and from 1.5 cells/µL to 0.2 cells/µL, p=0.001, respectively). For these B cell populations, similar observations were made for tacrolimus-treated patients. After in vitro re-stimulation with donor antigen, a 10-fold increase of TFH cells was observed, which was ~30% inhibited by belatacept, p=0.001, and ~50% by tacrolimus, p