Monocyte Subsets Responsible for Immunoglobulin G-Dependent Effector Functions In Vivo

Immunoglobulin G (IgG) antibodies confer protection against pathogenic microorganisms, serve as therapeutics in tumor therapy, and are involved in destruction of healthy tissues during autoimmune diseases. Understanding the molecular pathways and effector cell types involved in antibody-mediated effector functions is a prerequisite to modulate these activities. In this study we used two independent model systems to identify innate immune effector cells required for IgG activity in vivo. We first defined the precise repertoire of receptors for the IgG Fc fragment (FcγR) on innate immune effector cells in the blood and on tissue-resident macrophage populations. Despite expression of relevant activating FcγRs on various phagocyte populations, our data indicate that the majority of these cell types are dispensable for IgG activity in vivo. In contrast, IgG-dependent effector functions were selectively impaired in animals lacking the CX 3CR1 hiLy6C loCD11c int monocyte subset, which expressed the full set of FcγRs required for IgG activity. [Display omitted] ► Identification of precise FcγR repertoire on innate immune effector cells ► Tissue-resident phagocytes do not contribute to IgG effector functions ► Ly6C lo monocytes have the highest phagocytic activity during the steady state ► Ly6C lo monocytes are essential for autoantibody and therapeutic IgG activity