Abstract
Objective : Although IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, the pathogenesis remains unclear. Our recent studies demonstrated that the “grouped ddY mouse” is a useful model to approach the pathogenesis of IgAN because it shows disease progression with strong Th1 polarization. Moreover, serum levels of IgA/IgG2a immune complex were significantly correlated with the severity of glomerular lesions. Dysregulation of the mucosal immune response of IgAN patients has been discussed in this pathogenic process and mucosal dendritic cells (DCs) are key regulators of both T and B cell functions. Recent studies demonstrated that DCs directly regulate mature B cell responses at various stages of differentiation. Accordingly, the present study investigated the role of DCs through humoral immunity in ddY mice with the early stage of IgAN.
Materials and Methods : DCs from the spleens of diseased and quiescent ddY mice or B cells from normal BALB /c mice were prepared using a magnetic cell sorting system. Purified B cells were cocultured with the DCs isolated from diseased and quiescent ddY mice. IgA production in the supernatants was measured by ELISA, and we analyzed mRNA expression of APRIL and IL-6. Results : DCs from diseased ddY mice strongly induced B cells to produce higher levels of IgA than those from quiescent mice. Moreover, mRNA expressions of APRIL and IL-6 in DCs from diseased ddY mice were higher than those from quiescent ddY mice. Conclusion : The present data suggest that DCs may play key roles in the pathogenesis of murine IgAN through regulation of humoral immunity.
