The glycosylation of IgA produced by murine B cells is altered by Th2 cytokines.
We sought to determine whether selected cytokines, known to profoundly increase proliferation and/or production of Ig by B cells and their progeny, 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 cell differentiation. Glycosylation was assessed by detection with enzyme-lectin conjugates in an immunoabsorption assay and verified by profiling and sequencing of the N-linked oligosaccharides. Stimulation of B cells with IL-4 plus IL-5 significantly alters the terminal glycosylation of secreted IgA, whereas LPS has a minor effect, despite the fact that both stimuli are equipotent at inducing Ig class switching and Ig secretion. Moreover, the alteration in terminal glycosylation was more profound on IgA secreted from surface IgM+ than from surface IgA+ CH12LX cells. These results suggest that the increased production of IL-4 and IL-5 by peripheral blood lymphocytes from IgA nephropathy patients might result in the production of abnormally glycosylated IgA. In turn, this abnormally glycosylated IgA may promote deposition of IgA in glomeruli in this disease.
Chintalacharuvu
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SR
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Emancipator
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SN
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002846:Chromatography, Affinity; D006031:Glycosylation / Q000187:drug effects; D007070:Immunoglobulin A / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000032:analysis; D037121:Plant Lectins; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D054788:Ribosome Inactivating Proteins; D018418:Th2 Cells / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007070:Immunoglobulin A; D015848:Interleukin-5; D037102:Lectins; D008070:Lipopolysaccharides; D009005:Monosaccharides; D037121:Plant Lectins; D011994:Recombinant Proteins; C017707:Ricinus communis agglutinin-1; C050600:Sambucus nigra lectins; D015847:Interleukin-4; D054788:Ribosome Inactivating Proteins