title: Differential macrophage modulation of asymmetric IgG antibody synthesis by soluble or particulate stimuli.
abstract: Asymmetric IgG antibodies behave as antigen-blocking due to the presence of a mannose-rich oligosaccharide residue in one of the Fab fragments of the molecule. This feature prevents the interaction of this antibody with the antigenic epitope, then they are unable to activate of the immune effector mechanisms. Taking into account that macrophages modulate the adaptive immune response according to the nature of the stimulating antigen and that IL-6 increases the synthesis of asymmetric IgG, in this work we analysed the differential modulation of the synthesis of asymmetric IgG by culture supernatants from peritoneal macrophages (CSPM) stimulated with either OVA-polystyrene beads or soluble OVA. The levels of IL-10, IL-6 and TNFalpha were determined in CSPM to find elevated levels of IL-6 and TNFalpha only in those cultures stimulated with OVA-coated polystyrene beads. The 112D5 hybridoma was cultured in the presence of CSPM from cells stimulated with OVA-polystyrene beads or soluble OVA. There was an increase in the synthesis of asymmetric IgG only in those cultures of the hybridoma treated with CSPM stimulated with OVA-polystyrene beads this CSPM also had an antiproliferative effect on the hybridoma. A neutralizing anti-IL-6 antibody inhibited the synthesis of asymmetric IgG but could not revert the effect of such CSPM on the viability of the hybridoma. In addition, our results demonstrated that the murine TNFalpha, at a concentration similar to that found in the particle-stimulated CSPM, had an inhibitory effect on cell growth. In summary, IL-6 and TNFalpha are secreted at different concentrations by peritoneal macrophages depending upon the physicochemical nature of the stimulus, thus conditioning the humoral immune response elicited. The IL-6 present in the CSPM can regulate the secretion of asymmetric IgG and, together with TNFalpha can also regulate cell proliferation. Results obtained in this work would contribute to the knowledge of the role of macrophages in the modulation of the quality of the humoral immune response generated upon stimulation with particulate antigens.
authors.affiliation: Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IDEHU (CONICET-UBA), Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Apicella
authors.forename: Andrea
authors.initials: A
authors.lastname: Custidiano
authors.forename: Silvia
authors.initials: S
authors.lastname: Miranda
authors.forename: Lucía
authors.initials: L
authors.lastname: Novoa
authors.forename: José
authors.initials: J
authors.lastname: Dokmetjian
authors.forename: Teresa
authors.initials: T
authors.lastname: Gentile
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011137:Polystyrenes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D015850:Interleukin-6; D011137:Polystyrenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010047:Ovalbumin