Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers

Petrušić, Vladimir; Živković, Irena; Stojanović, Marijana; Stojićević, Ivana; Marinković, Emilija; Inić-Kanada, Aleksandra; Dimitijević, Ljiljana

doi:10.1007/s12026-011-8236-8

Cited by 13 publications

(9 citation statements)

References 43 publications

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“…Together with TEK, ANGPT1 has also been reported to be upregulated in psoriatic skin in humans (79). Elevated expression of SPP1 in the skin of psoriatic patients has been reported, but the expression of SPP1 in lesional skin of AD patients was not observed (80). Hence the upregulated angiogenesis found in the present study comports with previous research.…”

Section: Discussionsupporting

confidence: 90%

The Effect of Atopic Dermatitis and Diet on the Skin Transcriptome in Staffordshire Bull Terriers

et al. 2020

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Canine atopic dermatitis (CAD) has a hereditary basis that is modified by interactions with the environment, including diet. Differentially expressed genes in non-lesional skin, determined by RNA sequencing before and after a dietary intervention, were compared between dogs with naturally occurring CAD (n = 4) and healthy dogs (n = 4). The dogs were fed either a common commercial heat-processed high carbohydrate food (kibble diet) (n = 4), or a non-processed high fat food (raw meat-based diet) (n = 4). At the end of the diet intervention, 149 differentially expressed transcripts were found between the atopic and healthy dogs. The main canonical pathways altered by the dysregulation of these genes were angiopoietin signaling, epidermal growth factor signaling, activation of angiogenesis, and alterations in keratinocyte proliferation and lipid metabolism. On the other hand, 33 differently expressed transcripts were found between the two diet groups, of which 8 encode genes that are annotated in the current version of the dog genome: immunoglobulin heavy constant mu (IGHM), immunoglobulin lambda-like polypeptide 5 (IGLL5), B-cell antigen receptor complex-associated protein beta chain (CD79B), polymeric immunoglobulin receptor (PIGR), cystathionine β-synthase (CBS), argininosuccinate synthase 1 (ASS1), secretory leukocyte peptidase inhibitor (SLPI), and mitochondrial ribosome recycling factor (MRRF). All genes were upregulated in the raw diet group. In conclusion the findings of this study suggest alterations in lipid and keratinocyte metabolism as well as angiogenesis in the skin of atopic dogs. Additionally, a possible enhancement of innate immunity and decrease in oxidative stress was seen in raw food fed dogs, which could have an important role in preventing hypersensitivities and disturbed immunity at young age.

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Section: Discussionsupporting

confidence: 90%

The Effect of Atopic Dermatitis and Diet on the Skin Transcriptome in Staffordshire Bull Terriers

et al. 2020

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“…Furthermore, in our system, both polyclonal (IgMh1 and IgMh2) and monoclonal (IgMm2 and IgMm3) formulations had inhibitory effects, whereas monoclonal IgMm1 failed to inhibit T cell responses. We thus hypothesized that the different properties may be due to structural characteristics of IgM, such as the presence of J chains, shown before to be essential for transcytosis (20), and the state of polymerization (2,21). Western blot analyses revealed high levels of J chain in polyclonal IgMh1 and IgMh2 and in monoclonal IgMm2, all inhibitory, whereas low levels of J chain were found in the poorly inhibitory IgMm1, but also in the inhibitory IgMm3, suggesting that the effect of IgM on T cells may not be dependent on J chain content.…”

Section: Discussionmentioning

confidence: 99%

Sialylation of N-Linked Glycans Influences the Immunomodulatory Effects of IgM on T Cells

Colucci

Stöckmann

Butera

et al. 2015

The Journal of Immunology

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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.

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“…The latter is unlikely, as polymerization was reported to be completed in the endoplasmic reticulum [19,21] whereas the processing of glycans occurs in the Golgi apparatus. It was also hypothesized that J-chain expression could be a mechanism for B-cells to regulate the amount of circulating hexamers [11] as a mode for combating more serious infections [76]. For this study, the hexamer was recombinantly produced in the absence of the J-chain sequence, so information on glycan-mediated assembly of the IgMs by the presence of this chain could not be obtained.…”

Section: Tail Piece Glycan Asn563mentioning

confidence: 99%

Site-SpecificN-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

Moh

Lin

Thaysen‐Andersen

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. Glycosylation is known to play an important role in IgG antibody structure and function. Polymeric IgM, the largest known antibody in humans, displays five potential N-glycosylation sites on each heavy chain monomer. IgM can exist as a pentamer with a connecting singly N-glycosylated J-chain (with a total of 51 glycosylation sites) or as a hexamer (60 glycosylation sites). In this study, the N-glycosylation of recombinant pentameric and hexameric IgM produced by the same human cell type and culture conditions was site-specifically profiled by RP-LC-CID/ETD-MS/ MS using HILIC-enriched tryptic and GluC glycopeptides. The occupancy of all putative N-glycosylation sites on the pentameric and hexameric IgM were able to be determined. Distinct glycosylation differences were observed between each of the five N-linked sites on the IgM heavy chains. While Asn171, Asn332, and Asn395 all had predominantly complex type glycans, differences in glycan branching and sialylation were observed between the sites. Asn563, a high mannose-rich glycosylation site that locates in the center of the IgM polymer, was only approximately 60% occupied in both the pentameric and hexameric IgM forms, with a difference in relative abundance of the glycan structures between the pentamer and hexamer. This study highlights the information obtained by characterization of the site-heterogeneity of a highly glycosylated protein of high molecular mass with quaternary structure, revealing differences that would not be seen by global glycan or deglycosylated peptide profiling.

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Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers

Cited by 13 publications

References 43 publications

The Effect of Atopic Dermatitis and Diet on the Skin Transcriptome in Staffordshire Bull Terriers

The Effect of Atopic Dermatitis and Diet on the Skin Transcriptome in Staffordshire Bull Terriers

Sialylation of N-Linked Glycans Influences the Immunomodulatory Effects of IgM on T Cells

Site-SpecificN-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

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