Induction of “wire-loop” lesions by murine monoclonal IgG3 cryoglobulins

摘要: We have recently demonstrated that an IgG3 rheumatoid factor (RF) monoclonal antibody (mAb), clone 6-19, derived from unmanipulated autoimmune MRL/MpJ-lpr/lpr mice, is able to generate cryoglobulins via a non-immunological Fc interaction, and induce acute glomerulonephritis associated with cryoglobulinemia. Using this experimental model, we characterized the glomerular lesions induced by 6-19 RF cryoglobulin, in particular ultrastructural localization of cryoglobulin deposits. Although their initial was confined mesangium, were progressively accumulated subendothelial spaces capillary walls, leading formation resembling "wire-loop" lesion characteristically described for lupus nephritis. In addition, found identical 6-19-J558 hybrid antibody, composed gamma 3 heavy chain J558 lambda 1 light chain, which loses activity, but retains activity. These results strongly suggest direct deposition itself, without involvement immune complex formation, generation classical characteristic similar generated one anti-DNA mAb (NZB x NZW)F1 two four unknown specificities, mice. The absence significant lesions, spite large amounts cryoglobulins, mice receiving suggests importance physicochemical property provoke lesions.