Intravenous immunoglobulin modulates the maturation of TLR 4-primed peripheral blood monocytes

Intravenous immunoglobulin (IgIV) has immune modulating effects on the differentiation and function of dendritic cells (DC). Peripheral blood CD14+ monocytes were induced to differentiate into immature DC with IL-4/GM-CSF. DC maturation was analyzed by flow cytometry, and function assessed for antigen uptake and antigen processing. IgIV added during the differentiation process induced immature DC to differentiate into a mature DC with increased expression of CD83 and CCR7. A "priming" step with low concentrations of LPS or other TLR agonists that utilize the myD88 signaling pathway was necessary to observe these changes. These modulated DCs had reduced antigen uptake, but exhibited increased antigen presentation. Treatment of the IgIV with pepsin to generate F(ab')2 fragments abrogated these effects on DC maturation and function. The enhanced differentiation of PBM into DC required two signals: an initial exposure to low concentrations of LPS followed by IVIG. The second signal with IVIG was Fc dependent.