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Molecular and Cellular Biology Sep 1982Using a hybridoma cell line which secretes hapten-specific immunoglobulin M (IgM), we have isolated a variety of mutants which produce abnormal immunoglobulin....
Using a hybridoma cell line which secretes hapten-specific immunoglobulin M (IgM), we have isolated a variety of mutants which produce abnormal immunoglobulin. Immunoglobulin was tested for the size and composition of the component heavy and light chains and for variable and constant region related functional and serological activities. Some mutants secrete IgM which seems to be defective in hapten binding; others make IgM which appears not to activate complement. Many of the mutants secrete monomeric as opposed to pentameric IgM. In some cases, the defect apparently correlates with structural alterations in the mu heavy chain: partial deletion, polypeptide addition, and abnormal glycosylation have been observed. These mutant cell lines provide a means of identifying the structural basis of IgM function and of studying the biochemistry of IgM synthesis and processing.
Topics: Animals; Binding Sites, Antibody; Complement Activation; Hybridomas; Immunoglobulin Constant Regions; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Immunoglobulin M; Immunoglobulin Variable Region; Mice; Mutation
PubMed: 6817080
DOI: 10.1128/mcb.2.9.1033-1043.1982 -
Clinical Microbiology and Infection :... Feb 2018Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato. The most frequent clinical manifestations are erythema migrans and Lyme... (Review)
Review
BACKGROUND
Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato. The most frequent clinical manifestations are erythema migrans and Lyme neuroborreliosis. Currently, a large volume of diagnostic testing for LB is reported, whereas the incidence of clinically relevant disease manifestations is low. This indicates overuse of diagnostic testing for LB with implications for patient care and cost-effective health management.
AIM
The recommendations provided in this review are intended to support both the clinical diagnosis and initiatives for a more rational use of laboratory testing in patients with clinically suspected LB.
SOURCES
This is a narrative review combining various aspects of the clinical and laboratory diagnosis with an educational purpose. The literature search was based on existing systematic reviews, national and international guidelines and supplemented with specific citations.
IMPLICATIONS
The main recommendations according to current European case definitions for LB are as follows. Typical erythema migrans should be diagnosed clinically and does not require laboratory testing. The diagnosis of Lyme neuroborreliosis requires laboratory investigation of the spinal fluid including intrathecal antibody production, and the remaining disease manifestations require testing for serum antibodies to B. burgdorferi. Testing individuals with non-specific subjective symptoms is not recommended, because of a low positive predictive value.
Topics: Antibodies, Bacterial; Borrelia burgdorferi; Clinical Laboratory Techniques; Humans; Immunoglobulin M; Lyme Disease
PubMed: 28887186
DOI: 10.1016/j.cmi.2017.08.025 -
Cancer Metastasis Reviews Mar 2023Cancer plasticity is now a recognized new hallmark of cancer which is due to disturbances of cell differentiation programs. It is manifested not only in various forms... (Review)
Review
Cancer plasticity is now a recognized new hallmark of cancer which is due to disturbances of cell differentiation programs. It is manifested not only in various forms like the best-known epithelial-mesenchymal transition (EMT) but also in vasculogenic and megakaryocytic mimicries regulated by EMT-specific or less-specific transcription factors such as HIF1a or STAT1/2. Studies in the past decades provided ample data that cancer plasticity can be manifested also in the expression of a vast array of immune cell genes; best-known examples are PDL1/CD274, CD47, or IDO, and we termed it immunogenic mimicry (IGM). However, unlike other types of plasticities which are epigenetically regulated, expression of IGM genes are frequently due to gene amplifications. It is important that the majority of the IGM genes are regulated by interferons (IFNs) suggesting that their protein expressions are regulated by the immune microenvironment. Most of the IGM genes have been shown to be involved in immune escape of cancers broadening the repertoire of these mechanisms and offering novel targets for immunotherapeutics.
Topics: Humans; Neovascularization, Pathologic; Neoplasms; Epithelial-Mesenchymal Transition; Adaptation, Physiological; Immunoglobulin M; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Tumor Microenvironment
PubMed: 36754910
DOI: 10.1007/s10555-023-10087-1 -
The New Microbiologica Jul 2019IgM-enriched immunoglobulins (e-IgM) may be useful in patients with severe acute bacterial infections. The evidence for the administration of e-IgM is not extensive and... (Review)
Review
IgM-enriched immunoglobulins (e-IgM) may be useful in patients with severe acute bacterial infections. The evidence for the administration of e-IgM is not extensive and a definitive consensus has never been reached on its best use in patients with acute infections as well as in critically ill patients. However, the official indication in several countries, including Italy, is quite wide and mainly refers to supportive treatment of patients with acute severe bacterial infections. A multidisciplinary meeting of Italian Experts in Infectious Diseases, Anesthesia and Critical Care, Pneumology, Microbiology and Oncohaematology aimed to produce a statement on the best practical methodological score that could improve the use of e-IgM in patients with different infections, variable severity of disease and etiology. The Expert Panel reviewed the literature and the available guidelines, discussed the experience and eventually proposed to adapt the PIRO score to the practical methodological needs of a simple tool that could guide the administration of e-IgM.
Topics: Bacterial Infections; Expert Testimony; Humans; Immunoglobulin M; Immunoglobulins, Intravenous; Italy; Sepsis
PubMed: 31157400
DOI: No ID Found -
Scientific Reports May 2019Described in several epithelial cancer cells, Tn- (GalNAcα1-O-Ser/Thr) and T- (Galβ3GalNAcα1-O-Ser/Thr) antigens are examples of tumor-associated antigens. Increased...
Described in several epithelial cancer cells, Tn- (GalNAcα1-O-Ser/Thr) and T- (Galβ3GalNAcα1-O-Ser/Thr) antigens are examples of tumor-associated antigens. Increased expression of Tn- and T-antigens is associated with tumor invasion and metastasis, and patients with high concentration of anti-Tn and anti-T antibodies have a more benign evolution of pathology. Asialofetuin (ASF) and ovine submaxillary mucin (OSM) are two glycoproteins that expose T- and Tn-antigen, respectively. In this work, using ASF or OSM we affinity-purified anti-T and anti-Tn antibodies from normal human plasma and tested their ability to specifically recognize tumor human tissues. Whereas purified anti-T antibodies (purity degree increase of 127-fold, and 22% recovery) were mainly IgG, for purified anti-Tn antibodies (purity degree enhancement of 125-fold, and 26% yield) the IgM fraction was predominant over the IgG one. IgG2 subclass was significantly enriched in both purified antibody samples. Purified antibodies did not bind normal human tissue (0/42), although recognized malignant tissues from different origin such as colon carcinoma (11/77 by anti-Tn; 7/79 by anti-T), breast carcinoma (10/23 by anti-Tn; 7/23 by anti-T), and kidney carcinoma (45/51 by anti-Tn; 42/51 by anti-T). Our results suggest that purified human anti-Tn and anti-T antibodies have a potential as anti-tumor therapeutic agents; restoring their levels in human sera could positively affect the evolution of patients with epithelial tumor pathologies.
Topics: Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Agents, Immunological; Asialoglycoproteins; Carcinoma; Cell Line, Tumor; Chromatography, Affinity; Drug Screening Assays, Antitumor; Fetuins; Humans; Immobilized Proteins; Immunoglobulin G; Immunoglobulin M; Mucins; Plasma
PubMed: 31147593
DOI: 10.1038/s41598-019-44601-9 -
British Medical Journal (Clinical... Sep 1984
Topics: Humans; Immunoglobulin G; Immunoglobulin M; Serologic Tests; Toxoplasmosis
PubMed: 6432196
DOI: 10.1136/bmj.289.6445.570 -
Frontiers in Immunology 2023Immunoglobulin M (IgM) is the largest antibody isotype with unique features like extensive glycosylation and oligomerization. Major hurdles in characterizing its...
Immunoglobulin M (IgM) is the largest antibody isotype with unique features like extensive glycosylation and oligomerization. Major hurdles in characterizing its properties are difficulties in the production of well-defined multimers. Here we report the expression of two SARS-CoV-2 neutralizing monoclonal antibodies in glycoengineered plants. Isotype switch from IgG1 to IgM resulted in the production of IgMs, composed of 21 human protein subunits correctly assembled into pentamers. All four recombinant monoclonal antibodies carried a highly reproducible human-type N-glycosylation profile, with a single dominant N-glycan species at each glycosite. Both pentameric IgMs exhibited increased antigen binding and virus neutralization potency, up to 390-fold, compared to the parental IgG1. Collectively, the results may impact on the future design of vaccines, diagnostics and antibody-based therapies and emphasize the versatile use of plants for the expression of highly complex human proteins with targeted posttranslational modifications.
Topics: Humans; Immunoglobulin G; SARS-CoV-2; COVID-19; Antibodies, Viral; Immunoglobulin M; Antibodies, Monoclonal; Recombinant Proteins
PubMed: 37359564
DOI: 10.3389/fimmu.2023.1147960 -
Blood Aug 2016Chronic lymphocytic leukemia (CLL) with unmutated (U-CLL) or mutated (M-CLL) immunoglobulin gene heavy-chain variable region (IGHV) displays different states of anergy,...
Chronic lymphocytic leukemia (CLL) with unmutated (U-CLL) or mutated (M-CLL) immunoglobulin gene heavy-chain variable region (IGHV) displays different states of anergy, indicated by reduced surface immunoglobulin M (sIgM) levels and signaling, consequent to chronic (super)antigen exposure. The subsets also differ in the incidence of high-risk genetic aberrations and in DNA methylation profile, preserved from the maturational status of the original cell. We focused on sIgM expression and function, measured as intracellular Ca(2+) mobilization following stimulation, and probed correlations with clinical outcome. The relationship with genetic features and maturation status defined by DNA methylation of an 18-gene panel signature was then investigated. sIgM levels/signaling were higher and less variable in U-CLL than in M-CLL and correlated with disease progression between and within U-CLL and M-CLL. In U-CLL, increased levels/signaling associated with +12, del(17p) or NOTCH1 mutations. In M-CLL, there were fewer genetic lesions, although the methylation maturation status, generally higher than in U-CLL, varied and was increased in cases with lower sIgM levels/signaling. These features revealed heterogeneity in M-CLL and U-CLL with clear clinical correlations. Multivariate analyses with phenotype, genetic lesions, or DNA methylation maturation status identified high sIgM levels as a new potential independent factor for disease progression. Multiple influences on sIgM include the cell of origin, the clonal history of antigen encounter in vivo, and genetic damage. This simple marker compiles these different factors into an indicator worthy of further investigations for prediction of clinical behavior, particularly within the heterogeneous M-CLL subset.
Topics: Calcium; DNA Methylation; Disease Progression; Gene Expression Regulation, Leukemic; Humans; Immunoglobulin Heavy Chains; Immunoglobulin M; Immunoglobulin Variable Region; Leukemia, Lymphocytic, Chronic, B-Cell; Mutation; Receptor, Notch1
PubMed: 27301861
DOI: 10.1182/blood-2016-03-707786 -
Proceedings of the National Academy of... Oct 1983The rearranged immunoglobulin heavy (mu) and light (kappa) chain genes cloned from the Sp6 hybridoma cell line producing immunoglobulin M specific for the hapten 2,4,...
The rearranged immunoglobulin heavy (mu) and light (kappa) chain genes cloned from the Sp6 hybridoma cell line producing immunoglobulin M specific for the hapten 2,4, 6-trinitrophenyl were inserted into the transfer vector pSV2-neo and introduced into various plasmacytoma and hybridoma cell lines. The transfer of the mu and kappa genes resulted in the production of pentameric, hapten-specific, functional IgM.
Topics: Animals; Gene Expression Regulation; Genetic Vectors; Hybridomas; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Immunoglobulin M; Immunoglobulin kappa-Chains; Immunoglobulin mu-Chains; Mice; Plasmacytoma; Transfection
PubMed: 6312453
DOI: 10.1073/pnas.80.20.6351 -
BMB Reports Apr 2017Alternations in usage of polyadenylation sites during transcription termination yield transcript isoforms from a gene. Recent findings of transcriptome-wide alternative... (Review)
Review
Alternations in usage of polyadenylation sites during transcription termination yield transcript isoforms from a gene. Recent findings of transcriptome-wide alternative polyadenylation (APA) as a molecular response to changes in biology position APA not only as a molecular event of early transcriptional termination but also as a cellular regulatory step affecting various biological pathways. With the development of high-throughput profiling technologies at a single nucleotide level and their applications targeted to the 3'-end of mRNAs, dynamics in the landscape of mRNA 3'-end is measureable at a global scale. In this review, methods and technologies that have been adopted to study APA events are discussed. In addition, various bioinformatics algorithms for APA isoform analysis using publicly available RNA-seq datasets are introduced. [BMB Reports 2017; 50(4): 201-207].
Topics: 3' Untranslated Regions; Algorithms; Animals; High-Throughput Nucleotide Sequencing; Humans; Immunoglobulin M; Polyadenylation; RNA, Messenger; Sequence Analysis, RNA; Tetrahydrofolate Dehydrogenase; Transcription, Genetic; Transcriptome
PubMed: 28148393
DOI: 10.5483/bmbrep.2017.50.4.019