Dendritic cells of IgA nephropathy patients have an impaired capacity to induce IgA production in naïve B cells.
BACKGROUND
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, characterized by mesangial IgA1 deposits. We have previously demonstrated that IgAN patients have a hampered IgA immune response after mucosal challenge with a neoantigen. Dendritic cells are critically involved in the initiation of humoral immune responses, not only via activation of T-helper cells, but also via direct effect on naïve B cells. The aim of this study was to investigate the capacity of dendritic cells from IgAN patients to regulate IgA production.


METHODS
Dendritic cells were generated by culturing monocytes for 7 days in the presence of interleukin (IL)-4 and granulocyte macrophage-colony-stimulating factor (GM-CSF). Dendritic cells from either IgAN patients (N= 12) or controls (N= 12) were cultured for 14 days with naïve B cells in the presence of CD40L-transfected mouse fibroblasts (L-CD40L cells) and medium with or without IL-2 or IL-10. Supernatants were tested for the presence of immunoglobulins by specific enzyme-linked immunosorbent assay (ELISA).


RESULTS
In the presence of CD40L and IL-10, dendritic cells were able to increase immunoglobulin production by naïve B cells. Dendritic cells of IgAN patients induced significantly (P= 0.026) less IgA production than dendritic cells of control persons (2.30 microg/mL vs. 5.24 microg/mL), whereas no differences were found in the IgG and IgM production. When dendritic cells were replaced by supernatant of CD40L-stimulated dendritic cells of patients and controls, IgA production was increased, but no difference was seen between the two groups.


CONCLUSIONS
In the present study we show that dendritic cells of IgAN patients have an impaired capacity to induce IgA production in naïve B cells, which might explain the observed IgA hyporesponse upon mucosal challenge with a neoantigen.
Eijgenraam
Jan-Willem
JW
Department of Nephrology, Leiden University Medical Centre, Leiden, The Netherlands.
Woltman
Andrea M
AM
Kamerling
Sylvia W A
SW
Briere
Francine
F
de Fijter
Johan W
JW
Daha
Mohamed R
MR
van Kooten
Cees
C
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000378:metabolism*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000378:metabolism; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged
D017077:Culture Media, Conditioned; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D023201:CD40 Ligand