Particulate antigen, macrophage activation and modulation of the humoral immune response

APICELLA A; CUSTIDIANO A; MIRANDA S; GENTILE T

Córdoba

Congreso; VII Congreso Latinoamericano de Inmunología. .; 2005

Asociación Latinoamericana de Inmunología (ALAI) en conjunto con la Sociedad Argentina de Inmunología (SAI), la Sociedad Chilena de Inmunología (SOCHIN), la Sociedad Latinoamericana de Histocompatibilidad (SLAH) y el Grupo de Trabajo de Inmunología Pediát

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, thus preventing the activation 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 analyzed 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 TNFa were determined in CSPM to find elevated levels of IL-6 and TNFa 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 OVA, 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, suggesting that the antiproliferative effect could be attributed to TNFa. In summary, IL-6 and TNFa 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 TNFa 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.