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Human Plasma-derived Polymeric IgA and IgM Antibodies Associate with Secretory Component to Yield Biologically Active Secretory-like Antibodies
- Source :
- Journal of Biological Chemistry
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Immunotherapy with monoclonal and polyclonal immunoglobulin is successfully applied to improve many clinical conditions including infection autoimmune diseases or immunodeficiency. Most immunoglobulin products recombinant or plasma derived are based on IgG antibodies whereas to date the use of IgA for therapeutic application has remained anecdotal. In particular purification or production of large quantities of secretory IgA (SIgA) for potential mucosal application has not been achieved. In this work we sought to investigate whether polymeric IgA (plgA) recovered from human plasma is able to associate with secretory component (SC) to generate SIgA like molecules. We found that ~15 of plasma plgA carried J chain and displayed selective SC binding capacity either in a mixture with monomeric IgA (mlgA) or after purification. The recombinant SC associated covalently in a 1:1 stoichiometry with plgA and with similar efficacy as colostrum derived SC. In comparison with plgA the association with SC delayed degradation of SIgA by intestinal proteases. Similar results were obtained with plasma derived IgM. In vitro plasma derived IgA and SIgA neutralized Shigella flexneri used as a model pathogen resulting in a delay of bacteria induced damage targeted to polarized Caco 2 cell monolayers. The sum of these novel data demonstrates that association of plasma derived IgA or IgM with recombinant/colostrum derived SC is feasible and yields SIgA and SIgM like molecules with similar biochemical and functional characteristics as mucosa derived immunoglobulins. © 2013 by The American Society for Biochemistry and Molecular Biology Inc.
- Subjects :
- Secretory component
medicine.medical_treatment
Immunology
Passive immunity
Biology
Biochemistry
Shigella flexneri
Microbiology
law.invention
Plasma
03 medical and health sciences
0302 clinical medicine
law
Chlorocebus aethiops
medicine
Animals
Humans
Molecular Biology
030304 developmental biology
0303 health sciences
Cell Biology
Antibodies, Bacterial
Antibodies, Neutralizing
Recombinant Proteins
J chain
Secretory Component
3. Good health
Immunoglobulin M
Polyclonal antibodies
Immunoglobulin J-Chains
COS Cells
biology.protein
Recombinant DNA
Antibody
Immunoglobulin J Chain
030215 immunology
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 288
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....c49fe41246e617d2f92e4262140cd7e9