IVIg-mediated inhibition of antigen presentation: Predominant role of naturally occurring cationic IgG

The infusion of high doses of intravenous immunoglobulins (IVIg) produce anti-inflammatory effects in a diversity of autoimmune disorders. The need for such high doses suggests that only a small fraction of IgG is responsible for the anti-inflammatory effects. We recently showed that IVIg was internalized in APCs to compete with antigens for loading on MHC II molecules, leading to reduced antigen-specific T cell responses. Here we show that highly cationic IgG molecules present in IVIg are internalized more efficiently than IVIg in mouse P388D1 cells. We also show that the increased internalization correlates with the extent of inhibition of antigen presentation. Chemically cationized IVIg similarly showed improved internalization and inhibition of antigen presentation properties compared to IVIg. These observations suggest that highly cationic IgG are important mediators of the anti-inflammatory effects of IVIg resulting from inhibition of antigen presentation, such as the reduction in T cell activation and autoantibody production.

► The naturally cationic IgG fraction of IVIg is strongly internalized in APCs.
► Internalization level correlates with extent of antigen presentation inhibition.
► The inhibitory effect of cationic IgG is confirmed by chemical cationization.
► Highly cationic IgG contribute to the immunomodulatory effects of IVIg.