Unique B Cell Differentiation Profile in Tolerant Kidney Transplant Patients. Issue 1 (13th November 2013)

• Record Type: Journal Article
• Authors: Chesneau, M.; Pallier, A.; Braza, F.; Lacombe, G.; Le Gallou, S.; Baron, D.; Giral, M.; Danger, R.; Guerif, P.; Aubert‐Wastiaux, H.; Néel, A.; Michel, L.; Laplaud, D.‐A.; Degauque, N.; Soulillou, J.‐P.; Tarte, K.; Brouard, S.
• Is Part Of: American journal of transplantation. Volume 14:Issue 1(2014:Jan.)
• Page Start: 144
• Page End: 155
• Publication Date: 2013-11-13
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.12508
• Languages: English
• ISSNs: 1600-6135

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajt12508-sec-0001" sec-type="section"> <p>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 <italic>in vitro</italic> 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<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> transitional and CD20<sup>+</sup>CD38<sup>lo</sup>CD24<sup>lo</sup> naïve B cells compared to patients with stable graft function, correlating with a decreased frequency of CD20<sup>−</sup>CD38<sup>+</sup>CD138<sup>+</sup> 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 <italic>in vitro</italic> profile is consistent with down‐regulation of B cell differentiation genes and anti‐apoptotic B cell genes in these patients <italic>in vivo</italic>. 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.</p> </sec> </abstract>