TY - JOUR
T1 - Murine IgG1 and IgG3 isotype switch variants promote phagocytosis of Cryptococcus neoformans through different receptors
AU - Saylor, Carolyn A.
AU - Dadachova, Ekaterina
AU - Casadevall, Arturo
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Almost 3 decades ago, murine IgG3 was proposed to interact with a different receptor than the other IgG 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 FcγR and complement receptor blockage with specific Abs. IgG3 was an efficient opsonin for C. neoformans in FcγR- and CD18-deficient cells and in the presence of blocking Abs to FcγR 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 FcγRs.
AB - Almost 3 decades ago, murine IgG3 was proposed to interact with a different receptor than the other IgG 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 FcγR and complement receptor blockage with specific Abs. IgG3 was an efficient opsonin for C. neoformans in FcγR- and CD18-deficient cells and in the presence of blocking Abs to FcγR 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 FcγRs.
UR - http://www.scopus.com/inward/record.url?scp=73949111443&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73949111443&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0902752
DO - 10.4049/jimmunol.0902752
M3 - Article
C2 - 19949107
AN - SCOPUS:73949111443
SN - 0022-1767
VL - 184
SP - 336
EP - 343
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -