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Increased CD40 ligation and reduced BCR signalling leads to higher IL-10 production in B-cells from tolerant kidney transplant patients

Research output: Contribution to journalArticle

Original languageEnglish
Article numberTPA-2016-0165R1
JournalTransplantation
DOIs
Publication statusPublished - 28 Jul 2016

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King's Authors

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.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially.

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