Children with chronic renal failure have reduced numbers of memory B cells

Abstract

Reduced serum IgG and subclass levels have been demonstrated in children with chronic renal failure. To study possible causes of this reduction, we analysed B cell subset composition, T helper cell frequencies and immunoglobulin (Ig) production capacity in vitro in children with chronic renal failure, with or without dialysis treatment. B cell subsets were characterized by determining CD27, IgM, IgD and CD5 expression within the CD19(+) population. Intracellular expression of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 in PMA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) was used to evaluate T helper frequencies. The capacity of B cells to secrete Ig in vitro was determined by measuring IgG(1), IgG(2) and IgM in culture supernatants of anti-CD2/CD28 monoclonal antibody (MoAb)- or SAC/IL-2-stimulated PBMC. Memory B cell numbers (identified as percentage or absolute number of CD19(+) IgM-IgD- or CD19(+)CD27(+) lymphocytes) were lower in children treated with haemodialysis (HD), peritoneal dialysis (PD) and children with chronic renal failure before starting dialysis treatment (CRF) compared to healthy controls (HC) (P < 0.05). Compared with HC, CD5(+) (naive) B cells were reduced in HD-treated patients but not for PD or for children with chronic renal failure before starting dialysis treatment (CRF). No significant differences in CD4(+) T helper cell subsets were found between the groups. However, CRF children had a higher percentage of IFN-gamma producing CD8(+) T lymphocytes compared to HC (P = 0.02). Finally, IgG(1), IgG(2) and IgM production in vitro was similar in the four groups. In conclusion, significantly lower numbers of memory type B cells were found in children with chronic renal failure compared to healthy controls. This reduction may contribute to the low Ig levels found in these children.

Fig. 1

The percentage of IgM¯/IgD¯, CD27⁺ and CD5⁺ lymphocytes of total B cells in patients and healthy controls (HC). PD, peritoneal dialysis; HD haemodialysis; CRF, chronic renal failure, not yet dialysed. *P < 0·05, **P < 0·01.

Fig. 2

The longitudinal follow-up of the percentage of IgM¯/IgD¯ lymphocytes of total B cells during the first year of peritoneal dialysis (PD) treatment in four children.

Fig. 3

The percentage of of T cell subsets (CD4⁺or CD8⁺) producing TH1-type cytokines (IFN-γ and IL-2) or TH2-type cytokines (IL-4). *P < 0·05.