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Lymphocyte antigen 6G (Ly6G) is a 21-25 kDa glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the Ly-6/uPAR superfamily (UniProt P35461). It is expressed almost exclusively on mature neutrophils and their precursors in the bone marrow and peripheral tissues of mice, making it a definitive marker for murine granulocytes (Daley et al., 2008, J Leukoc Biol). Ly6G plays a significant role in regulating neutrophil migration and signaling during inflammatory responses, although its specific physiological ligands are not fully characterized (Lee et al., 2013, J Leukoc Biol). In preclinical research, Ly6G is a primary target for experimental neutrophil depletion using monoclonal antibodies like clone 1A8, which is highly specific to Ly6G compared to the Gr-1 antibody (clone RB6-8C5) that also targets Ly6C. Targeting Ly6G allows researchers to investigate the role of neutrophils in various disease states, including cancer-associated immunosuppression mediated by myeloid-derived suppressor cells (MDSCs), sepsis, and autoimmune inflammation. While Ly6G is a critical tool in mouse models, it is important to note that it lacks a direct human ortholog, which limits its direct translation as a clinical therapeutic target but reinforces its value in mechanistic immunology. The use of anti-Ly6G antibodies in vivo typically results in rapid and sustained depletion of circulating neutrophils, providing a model for studying neutropenia and innate immune deficiency.
Antibody-mediated depletion of neutrophils via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), or functional blockade of neutrophil recruitment.
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