Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression

Nephrol Dial Transplant. 2010 Jan;25(1):205-12. doi: 10.1093/ndt/gfp397. Epub 2009 Aug 14.


Background: End-stage renal disease (ESRD) results in increased susceptibility to infections, impaired response to vaccination and diffuse B-cell lymphopenia. However, the precise nature and mechanism of ESRD-induced B-cell lymphopenia remains unclear. Therefore, we studied the distribution of major B-cell subsets, B-cell growth, differentiation and survival factors, IL-7 and BAFF, and their receptors in 21 haemodialysis patients and 21 controls.

Methods: Innate B1 cells (CD19+, CD5+), conventional B2 cells (CD19+, CD5-), newly formed transitional B cells (CD19+, CD10+, CD27-), naïve B cells (CD19+, CD27-) and memory B cells (CD19+, CD27+) and BAFF receptor were quantified by flow cytometry. Plasma IL-7, BAFF, IL-6, TNF-alpha and IL-10 were measured by ELISA.

Results: The ESRD group exhibited significant reductions of all B-cell subpopulations except for transitional B cells that were less severely affected. No significant difference was found in B-cell apoptosis between the ESRD and control groups. Moreover, plasma IL-7 and BAFF levels were elevated in ESRD patients, therefore excluding their deficiencies as a possible culprit. However, BAFF receptor expression was significantly reduced in transitional but not mature B cells in the ESRD group. Interestingly, B-cell activation with the TLR9 agonist resulted in significantly greater production of IL-6 and TNF alpha but not IL-10 in the ESRD group.

Conclusions: Thus, despite elevation of B-cell growth, differentiation and survival factors, ESRD patients exhibited diffuse reduction of B-cell subpopulations. This was associated with the down-regulation of BAFF receptor in transitional B cells. The latter can, in part, contribute to B-cell lymphopenia by promoting resistance to the biological actions of BAFF that is a potent B-cell differentiation and survival factor.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / physiology
  • B-Cell Activating Factor / metabolism*
  • B-Cell Activation Factor Receptor / metabolism*
  • B-Lymphocyte Subsets / pathology*
  • B-Lymphocytes / pathology
  • Case-Control Studies
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-7 / metabolism*
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / pathology*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Renal Dialysis
  • Toll-Like Receptor 9 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Interleukin-6
  • Interleukin-7
  • TNFSF13B protein, human
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha