Production of Human Monoclonal Rheumatoid Factor Secreting Hybridomas Derived from Rheumatoid Synovial Cells

摘要

Although the cellular arm of the immune system is undoubtedly important in the pathogenesis of rheumatoid arthritis (RA), RA is an autoimmune extravascular immune complex disease involving synovium and interstitial tissues. The major autoantibody present is rheumatoid factor (RF), a polyclonal autoantibody directed to the Fc portion of IgG. Several observations point to RF-IgG complexes and their subsequent activation of complement as being important in the pathogenesis of RA. RF are heterogeneous in many qualitative characteristics including complement activating properties, specificity and avidity. For example, exhaustive studies attempting to demonstrate unique antigenic determinants on IgG Fc towards which serum RF is directed have been inconclusive, although many RA serum RF react with an antigen in the Fc that binds staphylococcal protein A. Characterizing the molecular genetic basis of RF in RA could provide exciting new understanding of important genetic and triggering factors in RA. However, this has not been possible because of the polyclonality of RF in RA. Hybridoma technology should overcome these difficulties and allow more precise characterization of these polyclonal RF, but reports to date using peripheral blood lymphocytes (PBL) have described only limited success. We herein describe successful production of human monoclonal IgM RF (mRF) secreting hybridomas derived from rheumatoid synovial cells (RSC). Reprints. (kt)