THE GLYCOSYLATION OF IGA PRODUCED BY MURINE B-CELLS IS ALTERED BY TH2CYTOKINES

We sought to determine whether selected cytokines, known to profoundly increase proliferation and/or production of Ig by B cells and their p rogeny, also have as yet unrecognized effects upon IgA glycosylation, For these studies, we selected CH12LX mouse B lymphoma cells, a widely used model of B fell differentiation, Glycosylation was assessed by d etection with enzyme-lectin conjugates in an immunoabsorption assay an d verified by profiling and sequencing of the N-linked oligosaccharide s, Stimulation of B cells with IL-4 plus IL-5 significantly alters the terminal glycosylation of secreted IgA, whereas LPS has a minor effec t, despite the fact that both stimuli are equipotent at inducing Ig cl ass switching and Ig secretion, Moreover, the alteration in terminal g lycosylation was more profound on IgA secreted from surface IgM(+) tha n from surface IgA(+) CH12LX cells, These results suggest that the inc reased production of IL-4 and IL-5 by peripheral blood lymphocytes fro m IgA nephropathy patients might result in the production of abnormall y glycosylated IgA, In turn, this abnormally glycosylated IgA may prom ote deposition of IgA in glomeruli in this disease.