scholarly journals Biosynthesis of immunoglobulin A (IgA) and immunoglobulin M (IgM). Control of polymerization by J chain

1973 ◽  
Vol 136 (3) ◽  
pp. 607-609 ◽  
Author(s):  
R. M. E. Parkhouse ◽  
E. Della Corte
Keyword(s):  
Plasma Cell ◽  
Molecular Species ◽  
Culture Medium ◽  
Immunoglobulin A ◽  
Total Radioactivity ◽  
Immunoglobulin M ◽  
Relative Distribution ◽  
J Chain ◽  
Specific Rabbit ◽  
In Cells

Cell suspensions of mouse plasma-cell tumours secreting IgA (immunoglobulin A) and IgM (immunoglobulin M) were incubated with radioactive leucine for various periods of time. The secreted immunoglobulins were precipitated from the culture medium with specific rabbit antisera to determine the relative distribution of radioactivity among the different molecular species, and to estimate the fraction of total radioactivity in the J chain. For IgM-secreting cells there is a balanced synthesis of 7S subunits and J chains, and the secreted product is uniformly assembled to the pentamer. In cells secreting IgA, however, the results demonstrate that the pool of intracellular J chain is less than the intracellular IgA pool. The concentration of J chain is therefore limiting and is less than the requirement for complete polymerization. The major factor that determines whether an intracellular monomer is secreted as such or is polymerized with the addition of J chain is therefore the amount of intracellular J chain. When this is limiting, as it is in cells secreting IgA, then monomer will be secreted.

scholarly journals Biosynthesis of immunoglobulin A (IgA). Secretion and addition of carbohydrate to monomer and polymer forms of a mouse myeloma protein

1973 ◽  
Vol 136 (3) ◽  
pp. 589-596 ◽  
Author(s):  
E. Della Corte ◽  
R. M. E. Parkhouse
Keyword(s):  
Plasma Cell ◽  
Molecular Species ◽  
Specific Antibody ◽  
Early Stage ◽  
Immunoglobulin A ◽  
Carbohydrate Composition ◽  
Myeloma Protein ◽  
J Chain ◽  
Co Precipitation ◽  
Mouse Myeloma

Cell suspensions of mouse plasma-cell tumour MOPC 315 secreting predominantly IgA (immunoglobulin A) monomer and dimer were incubated with radioactive leucine, mannose, galactose and fucose for various periods of time. The amounts of secreted and intracellular immunoglobulins were measured by co-precipitation with specific antibody, and the molecular species present were assessed by electrophoresis in polyacrylamide gels. Analysis of the secreted myeloma protein demonstrated that monomer and dimer IgA molecules are identical with respect to carbohydrate composition and rate of secretion. Within the cell, the myeloma protein is almost entirely accounted for by monomer units which either leave the cell as such or are polymerized with the addition of J chain close to the time of secretion. The results support the concept of a stepwise addition of carbohydrate residues to IgA immunoglobulin during the process of secretion. Similar patterns of carbohydrate assembly were found for the monomer or dimer molecules. Mannose residues are added at an early stage, whereas fucose is added close to the time of secretion. Galactose is also added early, but some may also be incorporated at a later stage. Control of IgA polymerization is considered unlikely to reflect regulation at the level of carbohydrate addition, and it is suggested that the critical controlling factor is the J chain.

scholarly journals Biosynthesis of immunoglobulin A (IgA) and immunoglobulin M (IgM). Requirement for J chain and a disulphide-exchanging enzyme for polymerization

1973 ◽  
Vol 136 (3) ◽  
pp. 597-606 ◽  
Author(s):  
E. Della Corte ◽  
R. M. E. Parkhouse
Keyword(s):  
Gradient Centrifugation ◽  
Immunoglobulin A ◽  
Sucrose Density Gradient ◽  
Immunoglobulin M ◽  
Reductive Cleavage ◽  
Sucrose Density Gradient Centrifugation ◽  
Structural Requirement ◽  
J Chain ◽  
Polypeptide Chains ◽  
Polymeric Immunoglobulins

Mouse myeloma cells secreting 19S IgM (immunoglobulin M) (MOPC 104E and TEPC 183) or monomer and polymer IgA (immunoglobulin A) (MOPC 315) were incubated with radioactive leucine and the intracellular and secreted immunoglobulins and immunoglobulin subunits were prepared by preparative sucrose-density-gradient centrifugation. Samples were reduced in the presence or absence of isolated J chain, passed over Sephadex G-25 and then incubated at 37°C for 30min with or without a source of disulphide-interchange enzyme. The extent of reassembly of reduced subunits was then evaluated by electrophoresis in polyacrylamide gels. Provided that J chain and the disulphide-interchange enzyme were supplied, both IgM and IgA could be assembled from their respective subunits, obtained by reductive cleavage of polymeric forms. Under similar conditions, assembly of polymeric forms from intracellular or secreted 7S monomer subunits also occurred. Under these conditions polymerization was total, there being no residue of the monomeric form. Reassembly did not occur in the absence of either J chain or the enzyme. All of the J chain released from IgM by reductive cleavage was incorporated back into the reassembled polymer. The J chain is therefore likely to be an essential structural requirement for polymeric immunoglobulins. A variety of controls ruled out non-specific interactions, and further suggested that the amino acid sequence of polypeptide chains determines the specificity of polymerization. The fact that intracellular IgA and IgM monomer subunits known to be deficient in galactose and fucose can be completely polymerized suggests that the addition of carbohydrate does not control polymerization.

Effect of Some Metabolic Inhibitors on Vinblastine-Induced Ribosomal-Granular Material Complexes

1971 ◽  
Vol 29 ◽  
pp. 548-549
Author(s):  
Awtar Krishan ◽  
Dora Hsu
Keyword(s):  
Granular Material ◽  
Rna Synthesis ◽  
Culture Medium ◽  
Actinomycin D ◽  
Metabolic Inhibitors ◽  
Protein And Rna Synthesis ◽  
Apparent Reduction ◽  
Plant Alkaloids ◽  
In Cells

Cells exposed to antitumor plant alkaloids, vinblastine and vincristine sulfate have large proteinacious crystals and complexes of ribosomes, helical polyribosomes and electron-dense granular material (ribosomal complexes) in their cytoplasm, Binding of H3-colchicine by the in vivo crystals shows that they contain microtubular proteins. Association of ribosomal complexes with the crystals suggests that these structures may be interrelated.In the present study cultured human leukemic lymphoblasts (CCRF-CEM), were incubated with protein and RNA-synthesis inhibitors, p. fluorophenylalanine, puromycin, cycloheximide or actinomycin-D before the addition of crystal-inducing doses of vinblastine to the culture medium. None of these compounds could completely prevent the formation of the ribosomal complexes or the crystals. However, in cells pre-incubated with puromycin, cycloheximide, or actinomycin-D, a reduction in the number and size of the ribosomal complexes was seen. Large helical polyribosomes were absent in the ribosomal complexes of cells treated with puromycin, while in cells exposed to cycloheximide, there was an apparent reduction in the number of ribosomes associated with the ribosomal complexes (Fig. 2).

scholarly journals Investigations of the structural function of the J chain in human immunoglobulin M

1973 ◽  
Vol 131 (4) ◽  
pp. 677-682 ◽  
Author(s):  
Manuel J. Ricardo ◽  
Franklin P. Inman
Keyword(s):  
Gel Filtration ◽  
Elution Curve ◽  
Immunoglobulin M ◽  
Human Immunoglobulin ◽  
Structural Function ◽  
J Chain ◽  
Mild Reduction

Human IgM molecules were treated with Na2SO3 or mercaptoethylamine in concentrations ranging from 2 to 14mm or 2 to 22mm respectively. The dissociation of IgM to IgMs varied from 0% to 100%. At the intermediate concentrations of either reagent the amount of freed J chains was less than expected. In an attempt to find an explanation for this, IgM was partially dissociated to IgMs with mercaptoethylamine. The IgMs isolated by gel filtration was divided according to the ascending and descending portions of the elution curve. These portions were treated with 24mm-mercaptoethylamine and analysed for the presence of J chains. Only the ascending portion contained free J chains. Thus, after mild reduction where not all the IgM molecules are dissociated to IgMs, some J chains remain covalently attached to some IgMs molecules although most of the J chains are freed. It was concluded that the J chain could serve as a ‘hitch’ for IgMs molecules forming intact IgM.

scholarly journals Culture Medium Supplements Derived from Human Platelet and Plasma: Cell Commitment and Proliferation Support

2017 ◽  
Vol 5 ◽  
Author(s):  
Anita Muraglia ◽  
Van Thi Nguyen ◽  
Marta Nardini ◽  
Massimo Mogni ◽  
Domenico Coviello ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Culture Medium ◽  
Human Platelet ◽  
Cell Commitment

scholarly journals Role of Serum Mycoplasma pneumoniae IgA, IgM, and IgG in the Diagnosis of Mycoplasma pneumoniae-Related Pneumonia in School-Age Children and Adolescents

2016 ◽  
Vol 24 (1) ◽  
Author(s):  
Wei-Ju Lee ◽  
Eng-Yen Huang ◽  
Chih-Min Tsai ◽  
Kuang-Che Kuo ◽  
Yi-Chuan Huang ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Mycoplasma Pneumoniae ◽  
Immunoglobulin A ◽  
Fold Increase ◽  
Laboratory Diagnosis ◽  
Diagnostic Value ◽  
Immunoglobulin M ◽  
School Age Children ◽  
School Age ◽  
Content Type

ABSTRACT Mycoplasma pneumoniae is an important causative pathogen of community-acquired pneumonia in children. Rapid and reliable laboratory diagnosis of M. pneumoniae infection is important so that appropriate antibiotic treatment can be initiated to reduce the misuse of drugs and resistance rates. Anti-M. pneumoniae immunoglobulin M (IgM) is an indicator of recent primary infection but can persist for several months after initial infection. It has been suggested that anti-M. pneumoniae immunoglobulin A (IgA) can be a reliable indicator for recent M. pneumoniae infection in adults. We investigated the clinical diagnostic value of M. pneumoniae IgA in school-age children and adolescents with M. pneumoniae-related pneumonia. Eighty children with pneumonia and seropositive for M. pneumoniae IgM or with a 4-fold increase of anti-M. pneumoniae immunoglobulin G (IgG) were enrolled from May 2015 to March 2016. The titers of M. pneumoniae IgA, IgM, and IgG, the clinical features, and laboratory examinations of blood, C-reactive protein, and liver enzymes were analyzed. The initial positivity rates for M. pneumoniae IgM and IgA upon admission to the hospital were 63.6 and 33.8%, respectively. One week after admission, the cumulative positivity rates for M. pneumoniae IgM and IgA increased to 97.5 and 56.3%, respectively. Detection of M. pneumoniae IgM was more sensitive than detection of M. pneumoniae IgA for the diagnosis of M. pneumoniae-related pneumonia in school-age children and adolescents; however, paired sera are necessary for a more accurate diagnosis.

Clinicopathological characteristics of primary immunoglobulin A nephropathy with immunoglobulin M deposition

2021 ◽  
Author(s):  
Han Ouyang ◽  
Jian Wen ◽  
Kai Song ◽  
Huaying Shen
Keyword(s):  
Immunoglobulin A ◽  
Clinicopathological Characteristics ◽  
Immunoglobulin M ◽  
Endothelial Cell Proliferation ◽  
Negative Group ◽  
Immunoglobulin A Nephropathy ◽  
Positive Group ◽  
Renal Tubular ◽  
The Relationship ◽  
Ig G

IntroductionImmunoglobulin (Ig) G deposition in patients with IgA nephro­pathy (IgAN) often indicates poor prognosis, but the relationship between IgM deposition and the clinicopathology of IgAN remains controversial. The purpose of this study is to further understand the relationship between IgM deposition and IgAN, so as to provide a basis for clinical evaluation and treatment.Material and methodsWe included a total of 839 IgAN patients from the nephropathy departments of 2 hospitals; there were 162 IgM-positive patients and 677 IgM-negative patients. Clinical and pathological data were retrospectively analysed. In addition, a multifaceted comparison was made between the IgM-positive group and the IgM-negative group.ResultsThe serum albumin and IgG levels of the IgM-positive group were lower than those of the IgM-negative group, and the levels of low-density lipo­protein, 24 h proteinuria, and IgM were higher than those of the IgM-nega­tive group. The proportion of endothelial cell proliferation (E1), segmental sclerosis or adhesion (S1), and renal tubular interstitial score in the IgM-posi­tive group were all higher than those in the IgM-negative group. Immunofluo­rescence results showed that the proportion of IgM-positive combination and IgG and C1q deposition was higher than that in the IgM-negative group.ConclusionsImmunoglobulin A nephropathy patients with IgM deposition have relatively poor clinical biochemical indicators, and the degree of renal pathological damage is also relatively serious.

Accessibility of the promoter sequence in the J-chain gene is regulated by chromatin changes during B-cell differentiation

1986 ◽  
Vol 6 (11) ◽  
pp. 4031-4038
Author(s):  
M E Minie ◽  
M E Koshland
Keyword(s):  
B Cell ◽  
Early Stage ◽  
Promoter Sequence ◽  
Immunoglobulin M ◽  
Chain Gene ◽  
B Cell Differentiation ◽  
Cell Stage ◽  
J Chain ◽  
Lymphoid Lines ◽  
Nuclease Digestion

The gene for the immunoglobulin M (IgM)-polymerizing protein, the J chain, is activated when the mature B cell is triggered to secrete pentamer IgM. Activation of the gene was found to be associated with chromatin changes in a 240-base-pair region at the 5' end of the gene. Analyses of lymphoid lines showed that the 5' region was resistant to nuclease digestion at the immature B-cell stage; it became slightly more accessible in mature B cells and cells at an early stage in the IgM response and then displayed an open, hypersensitive structure in IgM-secreting cells. In addition, analyses of normal, mitogen-stimulated lymphocytes showed that the open hypersensitive structure was coinducible with J-chain gene expression. These results suggest that the 5' chromatin changes precede transcription, making control sequences within the site accessible to regulatory factors.

scholarly journals Rapid method to detect rubella immunoglobulin M and immunoglobulin A antibodies.

1975 ◽  
Vol 1 (2) ◽  
pp. 132-135 ◽  
Author(s):  
H Schmitz ◽  
H Shimizu ◽  
D Kampa ◽  
H W Doerr
Keyword(s):  
Rapid Method ◽  
Immunoglobulin A ◽  
Immunoglobulin M

scholarly journals Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin

2020 ◽  
Author(s):  
Yuxin Wang ◽  
Guopeng Wang ◽  
Yaxin Li ◽  
Hao Shen ◽  
Huarui Chu ◽  
...  
Keyword(s):  
Specific Interaction ◽  
Immunoglobulin A ◽  
Underlying Mechanism ◽  
Secretory Component ◽  
Secretory Immunoglobulin A ◽  
Immunoglobulin Receptor ◽  
J Chain ◽  
Cryo Electron Microscopy ◽  
Structural Insights ◽  
Secretory Immunoglobulin

AbstractSecretory Immunoglobulin A (SIgA) is the most abundant antibody at the mucosal surface. SIgA possesses two additional subunits besides IgA: the joining chain (J-chain) and secretory component (SC). SC is the ectodomain of the polymeric immunoglobulin receptor (pIgR), which functions to transport IgA to the mucosa. The underlying mechanism of how the J-chain and pIgR/SC facilitates the assembly and secretion of SIgA remains to be understood. During the infection of Streptococcus pneumoniae, a pneumococcal adhesin SpsA hijacks SIgA and unliganded pIgR/SC to evade host defense and gain entry to human cells. How SpsA specifically targets SIgA and pIgR/SC also remains unclear. Here we report a cryo-electron microscopy structure of the Fc region of human IgA1 (Fcα) in complex with J-chain and SC (Fcα-J-SC), which reveals the organization principle of SIgA. We also present the structure of Fcα-J-SC in complex with SpsA, which uncovers the specific interaction between SpsA and human pIgR/SC. These results advance the molecular understanding of SIgA and shed light on the pathogenesis of S. pneumoniae.

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