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Unique B cell differentiation profile in tolerant kidney transplant patients.

Abstract : Operationally tolerant patients (TOL) display a higher number of blood B cells and transcriptional B cell signature. As they rarely develop an allo-immune response, they could display an abnormal B cell differentiation. We used an in vitro culture system to explore T-dependent differentiation of B cells into plasma cells. B cell phenotype, apoptosis, proliferation, cytokine, immunoglobulin production and markers of differentiation were followed in blood of these patients. Tolerant recipients show a higher frequency of CD20(+) CD24(hi) CD38(hi) transitional and CD20(+) CD38(lo) CD24(lo) naïve B cells compared to patients with stable graft function, correlating with a decreased frequency of CD20(-) CD38(+) CD138(+) differentiated plasma cells, suggestive of abnormal B cell differentiation. B cells from TOL proliferate normally but produce more IL-10. In addition, B cells from tolerant recipients exhibit a defective expression of factors of the end step of differentiation into plasma cells and show a higher propensity for cell death apoptosis compared to patients with stable graft function. This in vitro profile is consistent with down-regulation of B cell differentiation genes and anti-apoptotic B cell genes in these patients in vivo. These data suggest that a balance between B cells producing IL-10 and a deficiency in plasma cells may encourage an environment favorable to the tolerance maintenance.
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Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Monday, April 7, 2014 - 2:07:07 PM
Last modification on : Thursday, December 8, 2022 - 12:01:55 PM

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Mélanie Chesneau, A. Pallier, F. Braza, Gersende Lacombe, S. Le Gallou, et al.. Unique B cell differentiation profile in tolerant kidney transplant patients.. American Journal of Transplantation, 2014, 14 (1), pp.144-55. ⟨10.1111/ajt.12508⟩. ⟨hal-00974748⟩



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