Journal
TRANSPLANTATION
Volume 101, Issue 3, Pages 541-547Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0000000000001341
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Funding
- CONICYT Bicentennial Becas-Chile, Chile
- Medical Research Council (MRC) [G0801537, 88245]
- Medical Research Council (MRC) (MRC Centre for Transplantation, MRC) [MR/J006742/1]
- Guy's and St Thomas' Charity [R080530, R090782]
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London
- European Union [HEALTH-F5-2010-260687, 305147: BIO-DrIM]
- Medical Research Council [MR/L022699/1, G0801537, MR/J006742/1] Funding Source: researchfish
- MRC [MR/L022699/1, G0801537] Funding Source: UKRI
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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 sex-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 Tcells compared with healthy controls. Furthermore, B cells from tolerant recipients had reduced extracellular signal-regulated kinase signalling after BCR-mediated activation compared with 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. Conclusions. Altogether, our data suggest that the altered response of B cells in tolerant recipients may contribute to long-term stable graft acceptance.
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