NDT Advance Access published online on August 14, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp397
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Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression
1 Division of Nephrology and Hypertension 2 Division of Basic and Clinical Immunology, University of California, Irvine, CA, USA
Correspondence and offprint requests to: Nosratola. D. Vaziri; E-mail: ndvaziri{at}uci.edu
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Abstract |
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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-
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.
Keywords: infection; immune system; inflammation; vaccination; antibody production
* The first two authors have contributed equally to this work.
Received for publication: 18. 3.09
Accepted in revised form: 14. 7.09