Tissue niche occupancy determines the contribution of fetal- versus bone-marrow-derived macrophages to IgG effector functions

• DOI: 10.1016/j.celrep.2024.113757
• Publication Date: 2024-02-13T21:19:20Z
• Authors: Miriam Wöhner; Sarah Brechtelsbauer; Niklas Friedrich; Christof Vorsatz; Johanna Bulang; Chunguang Liang; Lena Schorr; Alain Beschin; Martin Guilliams; Jeffrey Ravetch; Falk Nimmerjahn; Markus Biburger
• Keywords: Monocyte; Fc receptor

Understanding the mechanisms underlying cytotoxic immunoglobulin G (IgG) activity is critical for improving therapeutic antibody and inhibiting autoantibody-mediated tissue pathology. While prior research highlights important role of mononuclear phagocytic system removing opsonized target cells, it remains unclear which monocyte or macrophage subsets stemming from fetal post-natal bone-marrow (BM)-associated definitive hematopoiesis are involved in cell depletion. By using a titrated irradiation approach as well Kupffer-cell-specific deletion activated Fcγ receptor signaling, we establish conditions under contribution BM-derived monocytes versus yolk-sac-derived liver-resident macrophages to IgG can be studied. Our results demonstrate that originating either adult play central IgG-mediated depletion cells peripheral blood steady-state conditions, highlighting impact niche not origin activity.