Macrophages measure the ‘eat-me’ signal IgG to identify targets for phagocytosis. We tested if prior encounters with IgG influence mouse bone-marrow-derived macrophage appetite. IgG is recognized by the Fc Receptor. To temporally control Fc Receptor activation, we engineered an Fc Receptor that is activated by light-induced oligomerization of Cry2, triggering phagocytosis. Using this tool, we demonstrate that subthreshold Fc Receptor activation primes macrophages to be more sensitive to IgG in future encounters. Macrophages that have previously experienced subthreshold Fc Receptor activation eat more IgG-bound cancer cells. Increased phagocytosis occurs by two discrete mechanisms – a short- and long-term priming. Long-term priming requires new protein synthesis and Erk activity. These long-term transcriptional changes show an increase in immune response genes and a reprogramming of macrophages towards an M2 polarization. Short-term priming does not require new protein synthesis and correlates with an increase in Fc Receptor mobility. Our work demonstrates that IgG primes macrophages for increased phagocytosis, suggesting that therapeutic antibodies may become more effective after initial priming doses.

This dataset relates to the included RNAseq data in the Developmental Cell manuscript entitled: Prior Fc Receptor activation primes macrophages for increased sensitivity to IgG via long term and short term mechanisms.