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Scientific article
English

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

Published inAutoimmunity, vol. 17, no. 1, p. 13-21
Publication date1994
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
  • Animals
  • Antibodies, Monoclonal/ immunology/pharmacology
  • Antigen-Antibody Reactions
  • Antigens, Surface/chemistry/immunology/ physiology
  • Autoimmune Diseases/genetics/ immunology
  • Bone Marrow Cells
  • Cell Division/drug effects
  • Cell Line
  • Cytokines/ biosynthesis
  • Gene Expression Regulation
  • Immunoglobulin G/ immunology
  • Lymphoproliferative Disorders/genetics/ immunology
  • Mice
  • Mice, Inbred Strains/ immunology
  • Mice, Mutant Strains/ immunology
  • Receptors, IgG/chemistry/immunology/ physiology
  • Rheumatoid Factor
  • Signal Transduction
Affiliation Not a UNIGE publication
Citation (ISO format)
SAKIHAMA, T. et al. 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. In: Autoimmunity, 1994, vol. 17, n° 1, p. 13–21. doi: 10.3109/08916939409014654
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ISSN of the journal0891-6934
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