title: Intra-Golgi formation of IgM-glycosaminoglycan complexes promotes Ig deposition.
abstract: Immune complexes arise from interactions between secreted Ab and Ags in the surrounding milieu. However, it is not known whether intracellular Ag-Ab interactions also contribute to the formation of extracellular immune complexes. In this study, we report that certain murine B cell hybridomas accumulate intracellular IgM and release large, spherical IgM complexes. The complexes (termed "spherons") reach 2 μm in diameter, detach from the cell surface, and settle out of solution. The spherons contain IgM multimers that incorporate the J chain and resist degradation by endoglycosidase H, arguing for IgM passage through the Golgi. Treatment of cells with inhibitors of proteoglycan synthesis, or incubation of spherons with chondroitinase ABC, degrades spherons, indicating that spheron formation and growth depend on interactions between IgM and glycosaminoglycans. This inference is supported by direct binding of IgM to heparin and hyaluronic acid. We conclude that, as a consequence of IgM binding to glycosaminoglycans, multivalent IgM-glycan complexes form in transit of IgM to the cell surface. Intra-Golgi formation of immune complexes could represent a new pathogenic mechanism for immune complex deposition disorders.
authors.affiliation: Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Salar N
authors.initials: SN
authors.lastname: Khan
authors.forename: John V
authors.initials: JV
authors.lastname: Cox
authors.forename: Satoru K
authors.initials: SK
authors.lastname: Nishimoto
authors.forename: Ching
authors.initials: C
authors.lastname: Chen
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.forename: Linda M
authors.initials: LM
authors.lastname: Hendershot
authors.forename: Martin
authors.initials: M
authors.lastname: Weigert
authors.forename: Marko
authors.initials: M
authors.lastname: Radic
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D006025:Glycosaminoglycans / Q000276:immunology / Q000378:metabolism*; D006056:Golgi Apparatus / Q000276:immunology / Q000378:metabolism*; D007105:Immune Complex Diseases / Q000276:immunology / Q000378:metabolism*; D015151:Immunoblotting; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission
chemical_list: D000936:Antigen-Antibody Complex; D006025:Glycosaminoglycans; D007075:Immunoglobulin M