Intravenous immunoglobulin ameliorates ITP via activating Fcγ receptors on dendritic cells

Despite a more than 20-year experience of therapeutic benefit, the relevant molecular and cellular targets of intravenous immunoglobulin ( IVIg) in autoimmune disease remain unclear. Contrary to the prevailing theories of IVIg action in autoimmunity, we show that IVIg drives signaling through activating Fc gamma receptors ( Fc gamma R) in the amelioration of mouse immune thrombocytopenic purpura ( ITP). The actual administration of IVIg was unnecessary because as few as 105 IVIg-treated cells could, upon adoptive transfer, ameliorate ITP. IVIg did not interact with the inhibitory Fc gamma RIIB on the initiator cell, although Fc gamma RIIB does have a role in the late phase of IVIg action. Notably, only IVIg-treated CD11c(+) dendritic cells could mediate these effects. We hypothesize that IVIg forms soluble immune complexes in vivo that prime dendritic-cell regulatory activity. In conclusion, the clinical effects of IVIg in ameliorating ITP seem to involve the acute interaction of IVIg with activating Fc gamma R on dendritic cells.