Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression.
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.
Pahl
Madeleine V
MV
Division of Nephrology and Hypertension, University of California, Irvine, CA, USA.
Gollapudi
Sastry
S
Sepassi
Lili
L
Gollapudi
Pavan
P
Elahimehr
Reza
R
Vaziri
Nosratola D
ND
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D001402:B-Lymphocytes / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D015850:Interleukin-6; D015851:Interleukin-7; C505719:TNFSF13B protein, human; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha
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