title: Human Secretory IgM Antibodies Activate Human Complement and Offer Protection at Mucosal Surface.
abstract: IgM molecules circulate in serum as large polymers, mainly pentamers, which can be transported by the poly-Ig receptor (pIgR) across epithelial cells to mucosal surfaces and released as secretory IgM (SIgM). The mucosal SIgM molecules have non-covalently attached secretory component (SC), which is the extracellular part of pIgR which is cleaved from the epithelial cell membrane. Serum IgM antibodies do not contain SC and have previously been shown to make a conformational change from 'a star' to a 'staple' conformation upon reaction with antigens on a cell surface, enabling them to activate complement. However, it is not clear whether SIgM similarly can induce complement activation. To clarify this issue, we constructed recombinant chimeric (mouse/human) IgM antibodies against hapten 5-iodo-4-hydroxy-3-nitro-phenacetyl (NIP) and in addition studied polyclonal IgM formed after immunization with a meningococcal group B vaccine. The monoclonal and polyclonal IgM molecules were purified by affinity chromatography on a column containing human SC in order to isolate joining-chain (J-chain) containing IgM, followed by addition of excess amounts of soluble SC to create SIgM (IgM J+ SC+). These SIgM preparations were tested for complement activation ability and shown to be nearly as active as the parental IgM J+ molecules. Thus, SIgM may offer protection against pathogens at mucosal surface by complement-mediated cell lysis or by phagocytosis mediated by complement receptors present on effector cells on mucosa.
authors.affiliation: Department of Infectious Disease Immunology, Norwegian Institute of Public Health, Oslo, Norway.|School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: T E
authors.identifier: http://orcid.org/0000-0001-8877-8519
authors.initials: TE
authors.lastname: Michaelsen
authors.forename: S
authors.initials: S
authors.lastname: Emilsen
authors.affiliation: Department of Infectious Disease Immunology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: R H
authors.initials: RH
authors.lastname: Sandin
authors.affiliation: Department of Infectious Disease Immunology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: B K
authors.initials: BK
authors.lastname: Granerud
authors.affiliation: Department of Infectious Disease Immunology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Bratlie
authors.affiliation: Department of Infectious Disease Immunology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: O
authors.initials: O
authors.lastname: Ihle
authors.affiliation: Centre for Immune Regulation (CIR) University of Oslo, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Sandlie
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D016667:Bacterial Capsules / Q000276:immunology; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007075:Immunoglobulin M / Q000276:immunology*; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology; D009592:Nitrohydroxyiodophenylacetate / Q000276:immunology; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012635:Secretory Component / Q000276:immunology
chemical_list: D007075:Immunoglobulin M; D022401:Meningococcal Vaccines; D011993:Recombinant Fusion Proteins; D012635:Secretory Component; C039455:capsular polysaccharide, meningococcal group B; C033027:secretory IgM; D009592:Nitrohydroxyiodophenylacetate; D003165:Complement System Proteins