Role of galactosylation in the renal pathogenicity of murine immunoglobulin G3 monoclonal cryoglobulins

Cryoglobulin activity associated with murine immunoglobulin G3 (lgG3) has b een shown to play a significant role in the development of murine lupuslike glomerulonephritis. A fraction, but not all, lgG3 monoclonal antibodies ar e capable of inducing a severe acute lupuslike glomerulonephritis as a resu lt of direct localization of lgG3 cryoglobulins, suggesting the importance of qualitative features of cryoglobulins in their nephritogenic activities. Here a remarkable difference is shown in the renal pathogenicity of 2 muri ne lgG3 monoclonal cryoglobulins, identical in the amino acid sequences of their heavy and light chains but different in galactosylation patterns of o ligosaccharide side chains because of their synthesis in different myeloma cells. The antibody lacking the capacity to induce severe glomerulonephriti s displayed an increased proportion of galactosylated heavy chains. Changes in conformation, as revealed by gel filtration analysis, reduced cryoglobu lin activity, and accelerated clearance could account for the lack of the r enal pathogenicity of the more galactosylated variant. This observation pro vides a direct demonstration for the role of IgG galactosylation in the pat hogenic potential of cryoglobulins, (Blood, 2001;97:3537-3543) (C) 2001 by The American Society of Hematology.