AN AUTOIMMUNE MRL MP-LPR/LPR 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) m ouse has previously been shown to induce IL-3, TNF-alpha and IL-6 prod uction, and autocrine growth in an IL-3-dependent myeloid cell line, F DC-P2/185-4. In the present study, we have attempted to further define the molecular mechanism responsible for the 1G10-induced activation o f FDC-P2/185-4 cells. We have shown that 1G10 lacked anti-IgG1 rheumat oid factor activity, failing to generate self-associated immune comple xes. Since 1G10 stimulated cells in an Fc(gamma)R-dependent manner, it seems likely that cross-linking of a cell surface antigen and Fc gamm a R by 1G10 antibody is responsible for the stimulation of FDC-P2/185- 4 cells. Among several mAb specific to surface antigens expressed on F DC-P2/185-4 cells (MHC class I, LFA-1, and Fc gamma R), only a mAb spe cific to the a 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 tha t induced by 1G10. Immunoprecipitation analysis revealed that 1G10 rec ognized a polypeptide with a molecular mass of 140 kilodaltons (p140), which differed from Fc gamma R and from LFA-1 alpha chain. These resu lts suggest that cross-linking of not general but particular cell surf ace antigens and Fc gamma R stimulates FDC-P2/185-4 cells to produce c ytokines resulting in their proliferation.