Fig. 2. Downstream signalling events induced upon crosslinking of activating FcγRs by IgG immune complexes.

Multimeric IgG immune complexes engage multiple Fcγ receptors (FcγRs) through low-affinity, high-avidity interactions (step 1). Receptor crosslinking upon IgG immune complex binding triggers phosphorylation (P) of their immunoreceptor tyrosine activating motifs (ITAMs), which in turn leads to the activation of kinases of the SYK and SRC family (step 2), as well as activation of the protein kinase C (PKC) pathway, resulting in a rapid increase in intracellular Ca²⁺ levels following activation of Ca²⁺ channels (step 3). Kinase activation also leads to actin remodelling (step 4), which is critical for receptor internalization and phagocytosis of the IgG immune complex. At later stages, cellular activation is associated with activation of specific transcription factors such as p38 and Jun amino-terminal kinases (JNK) (step 5) that drive the expression and release of pro-inflammatory cytokines and chemokines (for example, tumour necrosis factor (TNF), IL-1β and IL-8) (step 6) that shape immune responses and alter the effector function, migration and survival of leukocytes.