Murine IgG1 and IgG3 Isotype Switch Variants Promote Phagocytosis of Cryptococcus neoformans through Different Receptors

Almost 3 decades ago, murine IgG3 was proposed to interact with a different receptor than the other JgG subclasses, but the issue remains unresolved. The question of whether a specific receptor exists for IgG3 is critically important for understanding Ab-mediated immunity against Cryptococcus neoformans, where the different isotypes manifest profound differences in protective efficacy. In this study, we revisited this question by analyzing IgG1- and IgG3-mediated phagocytosis with variable region-identical mAbs using mouse macrophages deficient in various receptors and in conditions of Fc gamma R and complement receptor blockage with specific Abs. IgG3 was an efficient opsonin for C. neoformans in Fc gamma R- and CD18-deficient cells and in the presence of blocking Abs to Fc gamma R and complement receptor. Like IgG1, IgG3-mediated phagocytosis was associated with fungal residence in a mature phagosome that was followed by intracellular replication and exocytosis events. We conclude that a specific receptor for IgG3 exists in mice that is structurally different from the known Fc gamma Rs. The Journal of Immunology, 2010, 184: 336-343.