The Role of Constant Region Carbohydrate in the Assembly and Secretion of Human IgD and IgA1

Gala, Françoise A.; Morrison, Sherie L.

doi:10.1074/jbc.m203258200

Cited by 53 publications

(33 citation statements)

References 56 publications

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“…Benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside, an inhibitor that blocks synthesis of O-linked hinge region glycans beyond the first GalNAc, did not significantly affect intracellular assembly and secretion of IgA1 (Gala and Morrison, 2002), suggesting that O-linked sugars probably have little influence on Ig assembly.…”

Section: Role Of Glycosylation In Iga Assembly and Secretionmentioning

confidence: 92%

Mucosal Immunoglobulins

Woof

2015

Mucosal Immunology

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Section: Role Of Glycosylation In Iga Assembly and Secretionmentioning

confidence: 92%

Mucosal Immunoglobulins

Woof

2015

Mucosal Immunology

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“…The glycan content ranges from 2 to 3% by weight for IgG to 12-14% for IgM, IgD and IgE. The glycans attached to the Igs are important for Ig solubility [16], subcellular transport and secretion [17], conformation [12], binding to Fc receptors [12], normal plasma clearance [18] and complement activation [11]. In this Fig.…”

Section: Introductionmentioning

confidence: 99%

Mannan binding lectin and its interaction with immunoglobulins in health and in disease

et al. 2006

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“…BADG was used as inhibitor of β1,3-galactosyltransferase (36). IgA1-secreting cell lines (1 × 10 6 cells) from IgAN patients and controls were cultured with or without 5 mM BADG dissolved with 3.7% methanol in RPMI 1640 medium supplemented with l-glutamine, 20% FCS, penicillin, and streptomycin.…”

Section: Figurementioning

confidence: 99%

IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1

Suzuki¹,

Moldoveanu²,

Hall³

et al. 2008

J. Clin. Invest.

192

340

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Aberrant glycosylation of IgA1 plays an essential role in the pathogenesis of IgA nephropathy. This abnormality is manifested by a deficiency of galactose in the hinge-region O-linked glycans of IgA1. Biosynthesis of these glycans occurs in a stepwise fashion beginning with the addition of N-acetylgalactosamine by the enzyme N-acetylgalactosaminyltransferase 2 and continuing with the addition of either galactose by β1,3-galactosyltransferase or a terminal sialic acid by a N-acetylgalactosamine-specific α2,6-sialyltransferase. To identify the molecular basis for the aberrant IgA glycosylation, we established EBV-immortalized IgA1-producing cells from peripheral blood cells of patients with IgA nephropathy. The secreted IgA1 was mostly polymeric and had galactose-deficient O-linked glycans, characterized by a terminal or sialylated N-acetylgalactosamine. As controls, we showed that EBV-immortalized cells from patients with lupus nephritis and healthy individuals did not produce IgA with the defective galactosylation pattern. Analysis of the biosynthetic pathways in cloned EBV-immortalized cells from patients with IgA nephropathy indicated a decrease in β1,3-galactosyltransferase activity and an increase in N-acetylgalactosamine-specific α2,6-sialyltransferase activity. Also, expression of β1,3-galactosyltransferase was significantly lower, and that of N-acetylgalactosamine-specific α2,6-sialyltransferase was significantly higher than the expression of these genes in the control cells. Thus, our data suggest that premature sialylation likely contributes to the aberrant IgA1 glycosylation in IgA nephropathy and may represent a new therapeutic target.

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The Role of Constant Region Carbohydrate in the Assembly and Secretion of Human IgD and IgA1

Cited by 53 publications

References 56 publications

Mucosal Immunoglobulins

Mucosal Immunoglobulins

Mannan binding lectin and its interaction with immunoglobulins in health and in disease

IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1

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