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An autoimmune MRL/Mp-Ipr/Ipr mouse-derived monoclonal IgG antibody stimulates cytokine production in bone-marrow-derived cell line by cross-linking of a cell surface antigen and Fc receptor

Sakihama, T.
Shirakura-Shibata, Y.
Akasu, F.
Iwamoto, Masahiro
Nakajima, Y.
Tasaka, K.
Published in Autoimmunity. 1994, vol. 17, no. 1, p. 13-21
Abstract An IgG1 mAb 1G10 derived from an autoimmune MRL/Mp-Ipr/Ipr (MRL/Ipr) mouse has previously been shown to induce IL-3, TNF-alpha and IL-6 production, and autocrine growth in an IL-3-dependent myeloid cell line, FDC-P2/185-4. In the present study, we have attempted to further define the molecular mechanism responsible for the 1G10-induced activation of FDC-P2/185-4 cells. We have shown that 1G10 lacked anti-IgG1 rheumatoid factor activity, failing to generate self-associated immune complexes. Since 1G10 stimulated cells in an Fc gamma R-dependent manner, it seems likely that cross-linking of a cell surface antigen and Fc gamma R by 1G10 antibody is responsible for the stimulation of FDC-P2/185-4 cells. Among several mAb specific to surface antigens expressed on FDC-P2/185-4 cells (MHC class I, LFA-1, and Fc gamma R), only a mAb specific to the alpha chain of LFA-1 alpha was able to induce the IL-3 and Fc gamma R-dependent proliferation of FDC-P2/185-4 cells, similar to that induced by 1G10. Immunoprecipitation analysis revealed that 1G10 recognized a polypeptide with a molecular mass of 140 kilodaltons (p140), which differed from Fc gamma R and from LFA-1 alpha chain. These results suggest that cross-linking of not general but particular cell surface antigens and Fc gamma R stimulates FDC-P2/185-4 cells to produce cytokines resulting in their proliferation.
Keywords AnimalsAntibodies, Monoclonal/ immunology/pharmacologyAntigen-Antibody ReactionsAntigens, Surface/chemistry/immunology/ physiologyAutoimmune Diseases/genetics/ immunologyBone Marrow CellsCell Division/drug effectsCell LineCytokines/ biosynthesisGene Expression RegulationImmunoglobulin G/ immunologyLymphoproliferative Disorders/genetics/ immunologyMiceMice, Inbred Strains/ immunologyMice, Mutant Strains/ immunologyReceptors, IgG/chemistry/immunology/ physiologyRheumatoid FactorSignal Transduction
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PMID: 8025211
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