Abstract

Background—An increased percentage of peripheral transitional B-cells producing IL-10 has been observed in patients tolerant to kidney allografts. In healthy volunteers, the balance between the CD40 and B-cell receptor (BCR) signalling modulated IL-10 production by B-cells, with stimulation via the BCR decreasing CD40-mediated-IL-10 production. In this study, we evaluate whether in tolerant kidney transplant patients the increased IL-10 production by B-cells was due to an altered CD40 and/or BCR signalling. Methods—B-cells obtained from a new cohort of tolerant renal transplant recipients and those from age- and gender-matched healthy volunteers, were activated via CD40 and BCR, either alone or in combination. Results—In tolerant patients we observed higher percentages of B-cells producing IL-10 after CD40 ligation and higher expression of CD40L on activated T-cells, compared to healthy controls. Furthermore, B-cells from tolerant recipients had reduced ERK signalling following BCR- mediated activation compared to healthy controls. In keeping with this, combining BCR signalling with CD40 ligation did not reduce IL-10 secretion as was observed in healthy control transitional B-cells. Conclusion—Altogether our data suggests that the altered response of B-cells in tolerant recipients may contribute to long-term stable graft acceptance.