title: Sialylation of N-linked glycans influences the immunomodulatory effects of IgM on T cells.
abstract: Human serum IgM Abs are composed of heavily glycosylated polymers with five glycosylation sites on the μ (heavy) chain and one glycosylation site on the J chain. In contrast to IgG glycans, which are vital for a number of biological functions, virtually nothing is known about structure-function relationships of IgM glycans. Natural IgM is the earliest Ig produced and recognizes multiple Ags with low affinity, whereas immune IgM is induced by Ag exposure and is characterized by a higher Ag specificity. Natural anti-lymphocyte IgM is present in the serum of healthy individuals and increases in inflammatory conditions. It is able to inhibit T cell activation, but the underlying molecular mechanism is not understood. In this study, to our knowledge, we show for the first time that sialylated N-linked glycans induce the internalization of IgM by T cells, which in turn causes severe inhibition of T cell responses. The absence of sialic acid residues abolishes these inhibitory activities, showing a key role of sialylated N-glycans in inducing the IgM-mediated immune suppression.
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital-Scientific Institute, 00165 Rome, Italy;
authors.forename: Manuela
authors.initials: M
authors.lastname: Colucci
authors.affiliation: GlycoScience Group, National Institute for Bioprocessing Research and Training, Dublin, Ireland;
authors.forename: Henning
authors.initials: H
authors.lastname: Stöckmann
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital-Scientific Institute, 00165 Rome, Italy;
authors.forename: Alessia
authors.initials: A
authors.lastname: Butera
authors.affiliation: Gene Expression-Microarrays Laboratory, Bambino Gesù Children's Hospital-Scientific Institute, 00165 Rome, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Masotti
authors.affiliation: Gene Expression-Microarrays Laboratory, Bambino Gesù Children's Hospital-Scientific Institute, 00165 Rome, Italy;
authors.forename: Antonella
authors.initials: A
authors.lastname: Baldassarre
authors.affiliation: Research Center, Bambino Gesù Children's Hospital-Scientific Institute, 00165 Rome, Italy;
authors.forename: Ezio
authors.initials: E
authors.lastname: Giorda
authors.affiliation: Confocal Microscopy Core Facility, Research Center, Bambino Gesù Children's Hospital-Scientific Institute, 00165 Rome, Italy; and.
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.affiliation: GlycoScience Group, National Institute for Bioprocessing Research and Training, Dublin, Ireland;
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, 20132 Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sitia
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital-Scientific Institute, 00165 Rome, Italy;
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital-Scientific Institute, 00165 Rome, Italy; marina.vivarelli@opbg.net.
authors.forename: Marina
authors.initials: M
authors.lastname: Vivarelli
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D006031:Glycosylation; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007155:Immunologic Factors; D056747:Immunomodulation; D008213:Lymphocyte Activation / Q000276:immunology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D007075:Immunoglobulin M; D007155:Immunologic Factors; D011134:Polysaccharides; D019158:N-Acetylneuraminic Acid