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.
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.
Sakihama
T
T
Department of Parasitology & Immunology, Yamanashi Medical College, Japan.
Shirakura-Shibata
Y
Y
Akasu
F
F
Iwamoto
M
M
Izui
S
S
Nakajima
Y
Y
Tasaka
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology*; D008817:Mice, Mutant Strains / Q000276:immunology*; D017452:Receptors, IgG / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D012217:Rheumatoid Factor; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D016207:Cytokines; D007074:Immunoglobulin G; D017452:Receptors, IgG; D012217:Rheumatoid Factor