Unique B cell differentiation profile in tolerant kidney transplant patients

Am J Transplant. 2014 Jan;14(1):144-55. doi: 10.1111/ajt.12508. Epub 2013 Nov 13.


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.

Keywords: Apoptosis; B cells; cytokine; differentiation; tolerance; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / immunology
  • Apoptosis / immunology*
  • B-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Down-Regulation
  • Female
  • Humans
  • Immune Tolerance / immunology*
  • Interleukin-10 / biosynthesis
  • Kidney Transplantation*
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Plasma Cells / cytology*


  • Antigens, CD
  • Interleukin-10