Widespread macrophage expression of FcRY enables IgY recycling in avian species.

Immunoglobulin G (IgG) persists in blood circulation longer than most plasma proteins through recycling by endothelial and immune cells, thereby supporting sustained humoral immunity. In contrast, the mechanism underlying the long persistence of blood immunoglobulin Y (IgY), the functional avian counterpart of mammalian IgG, is unknown. Avian FcRY, a mannose receptor family member, functions as an IgY receptor that transcytoses maternal blood IgY into chicks. However, whether FcRY contributes to IgY homeostasis within immune cells has not yet been established. We investigated the expression pattern of FcRY in chicken immune cells and the involvement of FcRY-expressing macrophages in IgY recycling. Histological analyses revealed that intracellular FcRY staining was widely detected in macrophages across multiple immune tissues, but not on T cells or IgA-producing plasma B cells. In the chicken macrophage cell line HD11, IgY was taken up from the culture medium, bound to intracellular FcRY, and was subsequently recycled back into the extracellular space in an IgY-specific manner. Notably, FcRY overexpression in HD11 cells enhanced IgY recycling. In conclusion, these findings identified macrophage-associated FcRY as a regulator of IgY recycling in avian species, potentially providing a target and strategy for enhancing circulating IgY levels and humoral immunity.