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Abstract: 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. [Copyright &y& Elsevier]

Abstract: Previous work from our laboratory revealed that IVIg interacted with intracellular proteins involved in antigen presentation in B cells, suggesting that IVIg might interfere with the process of antigen presentation in these cells. In the present work, we used an in vitro assay with ovalbumin as model antigen and showed that IVIg inhibited both BCR-dependent and BCR-independent antigen presentation. The inhibition could not be explained by a modulation of expression of MHC II molecules expressed on B cells and was shown to occur in an FcγRIIb-independent manner, suggesting that the events responsible for the inhibitory effect occur at the intracellular level. This was supported by the observation of a direct correlation between the level of spontaneous internalization of two different proteins (IVIg and HSA) and their inhibitory potential. The inhibition of B cell-mediated antigen presentation reported here may help explain some of the anti-inflammatory effects of IVIg observed in treated patients, such as a decrease in autoantibody production. [Copyright &y& Elsevier]