Novel functions for IgG in modulating immune highways and DC traffickingficking

Immune complexes modulate immune highways and DC trafficking Antibodies are critical for defence against infection but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). We demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. Using intravital two-photon microscopy, we observed that local administration of model IC or autoantibody-containing IC from patients with systemic lupus erythematosus (SLE), resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. Together, these data suggest an additional mechanism by which ICs might drive autoimmunity in SLE via the inappropriate localisation of autoantigen-bearing DC and may also have implications for boost strategies in vaccination