scholarly journals Structure of the Human Secretory Immunoglobulin M Core

2020 ◽  
Author(s):  
Nikit Kumar ◽  
Christopher P. Arthur ◽  
Claudio Ciferri ◽  
Marissa L. Matsumoto
Keyword(s):  
Mucosal Immunity ◽  
Secretory Component ◽  
Immunoglobulin M ◽  
Secretory Iga ◽  
Human Antibodies ◽  
Sequence Identity ◽  
J Chain ◽  
Binding Interface ◽  
Mucosal Secretions ◽  
Secretory Immunoglobulin

AbstractImmunoglobulins (Ig) A and M are the only human antibodies that form oligomers and undergo transcytosis to mucosal secretions via the polymeric Ig receptor (pIgR). When complexed with the J-chain (JC) and the secretory component (SC) of pIgR, secretory IgA and IgM (sIgA and sIgM) play critical roles in host-pathogen defense. Recently, we determined the structure of sIgA-Fc which elucidated the mechanism of polymeric IgA assembly and revealed an extensive binding interface between IgA-Fc, JC, and SC. Despite low sequence identity shared with IgA-Fc, IgM-Fc also undergoes JC-mediated assembly and binds pIgR. Here, we report the structure of sIgM-Fc and carryout a systematic comparison to sIgA-Fc. Our structural analysis reveals a remarkably conserved mechanism of JC-templated oligomerization and SC recognition of both IgM and IgA through highly a conserved network of interactions. These studies reveal the structurally conserved features of sIgM and sIgA required for function in mucosal immunity.

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.

Secretory Immunoglobulin a in Oral and Respiratory Passages in Man

1975 ◽  
Vol 84 (20_suppl) ◽  
pp. 1-23 ◽  
Author(s):  
Goro Mogi
Keyword(s):  
Immunoglobulin A ◽  
Secretory Component ◽  
Secretory Iga ◽  
Secretory Cells ◽  
Antigenic Relationship ◽  
Serum Iga ◽  
Human Colostrum ◽  
Specific Antisera ◽  
Antigenic Relationships ◽  
Secretory Immunoglobulin

Secretory IgA (SIgA) is the predominant immunoglobulin in certain external secretions and may have an important role in immunological mucosal resistance. SIgA differs in chemical and immunological properties from serum IgA. The present study was undertaken to investigate the antigenic relationship between SIgA, free secretory component (FSC) and serum IgA and the localization of SIgA as well as other immunological classes in tissues of oral and respiratory passages by use of immunofluorescence technique. SIgA and FSC were highly purified from human colostrum and rabbit anti-SIgA and anti-SC antisera were prepared. On the basis of antigenic relationships between SIgA, FSC and serum IgA, it was emphasized that individual specific antisera for SC and IgA and/or SIgA should be used in immunochemical or immunohistological investigations for SIgA. The present study failed to detect SC determinants in palatine and lingual tonsils. However, it was evident that cells present in the pharyngeal tonsillar epithelium contain SC determinants. SC molecules may be synthesized in certain secretory cells of mucous membrane and glandular epithelium and the combining of SC with IgA could occur in the cytoplasm of epithelial cells, the intercellular spaces and/or in the lumens of glandular acini and ductules.

scholarly journals Longan Pulp Polysaccharide Protects Systemic Immunity and Intestinal Immunity in Mice Induced by Cyclophosphamide

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 738-738
Author(s):  
Yajuan Bai ◽  
Mingwei Zhang
Keyword(s):  
Mucosal Immunity ◽  
Plasma Cells ◽  
Underlying Mechanism ◽  
Secretory Component ◽  
Secretory Iga ◽  
Intestinal Lumen ◽  
Mucosal Barrier ◽  
Intestinal Immunity ◽  
Systemic Immunity ◽  
Serum Iga

Abstract Objectives This study aimed to explore the effect of longan pulp polysaccharide (LP) on the systemic immunity and intestinal mucosal immunity with immunosuppressive mice. The synthesis processing and secretion of intestinal secretory IgA (SIgA) were investigated. Methods Serum IgA, IgG, IgM and intestinal SIgA were detected by ELISA. Genes involved in the synthesis and secretion of SIgA were detected by Q-PCR and western blot. Results LP increased the thymus index, spleen index, and serum IgA level in cyclophosphamide (CTX)-treated mice. SIgA secretion in intestinal lumen was increased by LP as well. The underlying mechanism comes down to the facts as follows: LP increased intestinal cytokines expression and TGFβRII that is associated with pathways of IgA class switch recombination (CSR). By improving protein expression of mucosal address in cell-adhesion molecule-1 (MAdCAM-1) and integrin α4β7, LP was beneficial to gut homing of IgA + plasma cells. LP increased IgA, polymeric immunoglobulin receptor (pIgR), and secretory component (SC) to fortify the SIgA secretion. Conclusions This study suggested that moderate consumption of LP is helpful for improving systemic immunity and intestinal mucosal immunity via promotion of intestinal SIgA to strengthen the mucosal barrier. Funding Sources This work was supported by the National Key Research Project of China (2018YFC1602105, 2019YFD1002304), Guangdong Provincial Science and Technology Project (2018A050506050), President Foundation of Guangdong Academy of Agricultural Sciences (201812B).

Structural insights into immunoglobulin M

Science ◽  
2020 ◽  
Vol 367 (6481) ◽  
pp. 1014-1017 ◽  
Author(s):  
Yaxin Li ◽  
Guopeng Wang ◽  
Ningning Li ◽  
Yuxin Wang ◽  
Qinyu Zhu ◽  
...  
Keyword(s):  
Mucosal Immunity ◽  
Molecular Mechanisms ◽  
Immunoglobulin M ◽  
Structural Basis ◽  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor ◽  
J Chain ◽  
Cryo Electron Microscopy ◽  
Large Conformational Change ◽  
Structural Insights

Immunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly and transport depend on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR), but the underlying molecular mechanisms of these processes are unclear. We report a cryo–electron microscopy structure of the Fc region of human IgM in complex with the J-chain and pIgR ectodomain. The IgM-Fc pentamer is formed asymmetrically, resembling a hexagon with a missing triangle. The tailpieces of IgM-Fc pack into an amyloid-like structure to stabilize the pentamer. The J-chain caps the tailpiece assembly and bridges the interaction between IgM-Fc and the polymeric immunoglobulin receptor, which undergoes a large conformational change to engage the IgM-J complex. These results provide a structural basis for the function of IgM.

Secretory Immunoglobulin a in Oral and Respiratory Passages in Man

1975 ◽  
Vol 84 (3_suppl) ◽  
pp. 2-23 ◽  
Author(s):  
Goro Mogi
Keyword(s):  
Immunoglobulin A ◽  
Secretory Component ◽  
Secretory Iga ◽  
Secretory Cells ◽  
Antigenic Relationship ◽  
Serum Iga ◽  
Human Colostrum ◽  
Specific Antisera ◽  
Antigenic Relationships ◽  
Secretory Immunoglobulin

Secretory IgA (SIgA) is the predominant immunoglobulin in certain external secretions and may have an important role in immunological mucosal resistance. SIgA differs in chemical and immunological properties from serum IgA. The present study was undertaken to investigate the antigenic relationship between SIgA, free secretory component (FSC) and serum IgA and the localization of SIgA as well as other immunological classes in tissues of oral and respiratory passages by use of immunofluorescence technique. SIgA and FSC were highly purified from human colostrum and rabbit anti-SIgA and anti-SC antisera were prepared. On the basis of antigenic relationships between SIgA, FSC and serum IgA, it was emphasized that individual specific antisera for SC and IgA and/or SIgA should be used in immunochemical or immunohistological investigations for SIgA. The present study failed to detect SC determinants in palatine and lingual tonsils. However, it was evident that cells present in the pharyngeal tonsillar epithelium contain SC determinants. SC molecules may be synthesized in certain secretory cells of mucous membrane and glandular epithelium and the combining of SC with IgA could occur in the cytoplasm of epithelial cells, the intercellular spaces and/or in the lumens of glandular acini and ductules.

scholarly journals Oral Immunotherapy With Human Secretory Immunoglobulin A Improves Survival in the Hamster Model of Clostridioides difficile Infection

2021 ◽  
Author(s):  
Estelle F Chiari ◽  
William Weiss ◽  
Michael R Simon ◽  
Stephan T Kiessig ◽  
Mark Pulse ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Passive Immunization ◽  
Secretory Component ◽  
Oral Immunotherapy ◽  
Secretory Iga ◽  
Hamster Model ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Secretory Immunoglobulin ◽  
Donor Plasma

Abstract Coadministration of human secretory IgA (sIgA) together with subtherapeutic vancomycin enhanced survival in the Clostridioides difficile infection (CDI) hamster model. Vancomycin (5 or 10 mg/kg × 5 days) plus healthy donor plasma sIgA/monomeric IgA (TID × 21 days) or hyperimmune sIgA/monomeric IgA (BID × 13 days) enhanced survival. Survival was improved compared to vancomycin alone, P = .018 and .039 by log-rank Mantel-Cox, for healthy and hyperimmune sIgA, respectively. Passive immunization with sIgA (recombinant human secretory component plus IgA dimer/polymer from pooled human plasma) can be administered orally and prevents death in a partially treated CDI hamster model.

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 Correlations between Antibody Immune Responses at Different Mucosal Effector Sites Are Controlled by Antigen Type and Dosage

2000 ◽  
Vol 68 (7) ◽  
pp. 3830-3839 ◽  
Author(s):  
Dörthe Externest ◽  
Barbara Meckelein ◽  
M. Alexander Schmidt ◽  
Andreas Frey
Keyword(s):  
Cholera Toxin ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Routine Diagnostics ◽  
Significant Relationships ◽  
Serum Igg ◽  
Mucosal Surfaces ◽  
Secretory Immunoglobulin

ABSTRACT Monitoring specific secretory immunoglobulin A (IgA) responses in the intestines after mucosal immunization or infection is impeded by the fact that sampling of small intestinal secretions requires invasive methods not feasible for routine diagnostics. Since IgA plasma cells generated after intragastric immunization are known to populate remote mucosal sites as well, secretory IgA responses at other mucosal surfaces may correlate to those in the intestines and could serve as proxy measures for IgA secretion in the gut. To evaluate the practicability of this approach, mice were immunized intragastrically with 0.2, 2, and 20 mg of ovalbumin plus 10 μg of cholera toxin, and the antigen-specific local secretory IgA responses in duodenal, ileal, jejunal, rectal, and vaginal secretions, saliva, urine, and feces, as well as serum IgG and IgA responses were analyzed by enzyme-linked immunosorbent assay. Correlation analysis revealed significant relationships between serum IgG and IgA, urinary IgA, salivary IgA, and secretory IgA in duodenal, jejunal, ileal, and rectal secretions for the 0.2-mg but not for the 20-mg ovalbumin dose. Fecal samples were poor predictors for intestinal antiovalbumin IgA responses, and no correlations could be established for cholera toxin, neither between local anti-cholera toxin levels nor to the antiovalbumin responses. Thus, specific IgA in serum, saliva, or urine can serve as a predictor of the release of specific IgA at intestinal surfaces after intragastric immunization, but the lack of correlations for high ovalbumin doses and for cholera toxin indicates a strong dependency on antigen type and dosage for these relationships.

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.

Depletion of gut secretory immunoglobulin A coated Lactobacillus reuteri is associated with gestational diabetes mellitus-related intestinal mucosal barrier damage

2021 ◽  
Author(s):  
Haowen Zhang ◽  
Ce Qi ◽  
Yuning Zhao ◽  
Mengyao Lu ◽  
Xinyue Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Lactobacillus Reuteri ◽  
Immunoglobulin A ◽  
Mucosal Damage ◽  
Secretory Iga ◽  
Mucosal Barrier ◽  
Secretory Immunoglobulin

Gestational diabetes mellitus (GDM) may be related to intestinal mucosal damage and inflammation-induced dysbiosis of secretory IgA (SIgA) coated microbiota. SIgA coated L. reuteri can reduce the level of inflammation of GDM in vitro.

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