TY - JOUR
T1 - Antibody-mediated modulation of Cryptococcus neoformans infection is dependent on distinct Fc receptor functions and IgC subclasses
AU - Yuan, Rui Rong
AU - Clynes, Raphael
AU - Oh, Jin
AU - Ravetch, Jeffrey V.
AU - Scharff, Matthew D.
PY - 1998/2/16
Y1 - 1998/2/16
N2 - Coupling of an antibody response to effector cells through the Fc region of antibodies is a fundamental objective of effective vaccination. We have explored the role of the Fc receptor system in a murine model of Cryptococcus neoformans protection by infecting mice deleted for the common γ chain of FcRs. Passive administration of an IgG1 mAb protects FcRγ(+/-) mice infected with C. neoformans, but fails to protect FcRγ(-/-) mice, indicating that the γ chain acting through FcγRI and/or III is essential for IgG1-mediated protection. In contrast, passive administration of an IgG3 mAb with identical specificity resulted in enhanced pathogenicity in γ chain-deficient and wild-type mice. In vitro studies with isolated macrophages demonstrate that IgG1-, IgG2a-, and IgG2b-opsonized C. neoformans are not phagocytosed or arrested in their growth in the absence of the FcRγ chain. In contrast, opsonization of C. neoformans by IgG3 does not require the presence of the γ chain or of FcRII, and the internalization of IgG3-treated organisms does not arrest fungal growth.
AB - Coupling of an antibody response to effector cells through the Fc region of antibodies is a fundamental objective of effective vaccination. We have explored the role of the Fc receptor system in a murine model of Cryptococcus neoformans protection by infecting mice deleted for the common γ chain of FcRs. Passive administration of an IgG1 mAb protects FcRγ(+/-) mice infected with C. neoformans, but fails to protect FcRγ(-/-) mice, indicating that the γ chain acting through FcγRI and/or III is essential for IgG1-mediated protection. In contrast, passive administration of an IgG3 mAb with identical specificity resulted in enhanced pathogenicity in γ chain-deficient and wild-type mice. In vitro studies with isolated macrophages demonstrate that IgG1-, IgG2a-, and IgG2b-opsonized C. neoformans are not phagocytosed or arrested in their growth in the absence of the FcRγ chain. In contrast, opsonization of C. neoformans by IgG3 does not require the presence of the γ chain or of FcRII, and the internalization of IgG3-treated organisms does not arrest fungal growth.
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U2 - 10.1084/jem.187.4.641
DO - 10.1084/jem.187.4.641
M3 - Article
C2 - 9463414
AN - SCOPUS:0032536375
SN - 0022-1007
VL - 187
SP - 641
EP - 648
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -