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-α 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. The Author 2009. Published by Oxford University Press [on behalf of the ERA-EDTA]. All rights reserved.2009Oxford University PressThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses?by-nc/2.0/uk/) which permits unrestricted non-commercial use distribution, and reproduction in any medium, provided the original work is properly cited.