Abstract
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 gamma chain of FcRs. Passive administration of an IgG1 mAb protects FcRgamma+/- mice infected with C. neoformans, but fails to protect FcRgamma-/- mice, indicating that the gamma chain acting through FcgammaRI 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 gamma 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 FcRgamma chain. In contrast, opsonization of C. neoformans by IgG3 does not require the presence of the gamma chain or of FcRII, and the internalization of IgG3-treated organisms does not arrest fungal growth.
MeSH Terms
Animals
Antibodies, Monoclonal/immunology
Antigen-Antibody Reactions
Cells, Cultured
Coculture Techniques
Cryptococcosis/immunology
Cryptococcus neoformans/growth & development
Female
Immunoglobulin G/classification,immunology
Macrophages/immunology,microbiology
Mice
Mice, Inbred C57BL
Phagocytosis
Receptors, Fc/immunology,physiology
Rosette Formation
Chemicals
Antibodies, Monoclonal
Immunoglobulin G
Receptors, Fc
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yuan R
Department of Cell Biology of the Albert Einstein College of Medicine, Bronx, New York, 10461, USA.
Clynes R
Oh J
Ravetch J V
Scharff M D
References (33)
33 references, click to expand
-
Fc receptor biology.
Annu Rev Immunol. 1997;15:203-34
PMID: 9143687
-
T cells cooperate with passive antibody to modify Cryptococcus neoformans infection in mice.
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2483-8
PMID: 9122221
-
Fc receptors are required in passive and active immunity to melanoma.
Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):652-6
PMID: 9435247
-
The Fc receptors of primary and cultured phagocytic cells studied with homogeneous antibodies.
J Immunol. 1978 Oct;121(4):1329-33
PMID: 701797
-
IgG1 and IgG2b share the Fc receptor on mouse macrophages.
J Immunol. 1980 Aug;125(2):631-3
PMID: 7391572
-
A new Fc receptor on mouse macrophages binding IgG3.
J Exp Med. 1981 Mar 1;153(3):514-9
PMID: 7252406
-
Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Diagnostic features and outcome of treatment.
Ann Intern Med. 1986 Feb;104(2):234-40
PMID: 3946951
-
Role of natural killer cells in resistance to Cryptococcus neoformans infections in mice.
Am J Pathol. 1987 Aug;128(2):354-61
PMID: 3618730
-
Function and regulation of a murine macrophage-specific IgG Fc receptor, Fc gamma R-alpha.
J Exp Med. 1988 Jun 1;167(6):1909-25
PMID: 2968434
-
A macrophage Fc gamma receptor and the mast cell receptor for IgE share an identical subunit.
Nature. 1989 Oct 26;341(6244):752-4
PMID: 2529442
-
A subunit common to an IgG Fc receptor and the T-cell receptor mediates assembly through different interactions.
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3837-41
PMID: 1827205
-
The mouse antibody response to infection with Cryptococcus neoformans: VH and VL usage in polysaccharide binding antibodies.
J Exp Med. 1991 Jul 1;174(1):151-60
PMID: 1676047
-
Fc receptors.
Annu Rev Immunol. 1991;9:457-92
PMID: 1910686
-
Overview of host defenses in fungal infections.
Clin Infect Dis. 1992 Mar;14 Suppl 1:S37-42
PMID: 1562693
-
Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain.
J Exp Med. 1992 May 1;175(5):1381-90
PMID: 1314888
-
Antibodies elicited by a Cryptococcus neoformans-tetanus toxoid conjugate vaccine have the same specificity as those elicited in infection.
J Infect Dis. 1992 Jun;165(6):1086-93
PMID: 1583327
-
Protective murine monoclonal antibodies to Cryptococcus neoformans.
Infect Immun. 1992 Nov;60(11):4534-41
PMID: 1398966
-
Complement defense mechanisms.
Curr Opin Immunol. 1993 Feb;5(1):83-9
PMID: 8452679
-
Signal transduction by Fc receptors: the Fc epsilon RI case.
Immunol Today. 1993 May;14(5):222-6
PMID: 8517921
-
FcR gamma chain deletion results in pleiotrophic effector cell defects.
Cell. 1994 Feb 11;76(3):519-29
PMID: 8313472
-
Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B.
Antimicrob Agents Chemother. 1994 Mar;38(3):580-7
PMID: 8203858
-
Fc receptors initiate the Arthus reaction: redefining the inflammatory cascade.
Science. 1994 Aug 19;265(5175):1095-8
PMID: 8066448
-
Fc receptors: rubor redux.
Cell. 1994 Aug 26;78(4):553-60
PMID: 8069908
-
Cryptococcus neoformans infection can elicit protective antibodies in mice.
Can J Microbiol. 1994 Oct;40(10):888-92
PMID: 8000967
-
Antibodies to Cryptococcus neoformans glucuronoxylomannan enhance antifungal activity of murine macrophages.
Infect Immun. 1995 Feb;63(2):573-9
PMID: 7822024
-
Isotype switching from IgG3 to IgG1 converts a nonprotective murine antibody to Cryptococcus neoformans into a protective antibody.
J Immunol. 1995 Feb 15;154(4):1810-6
PMID: 7836766
-
Molecular basis of Fc receptor function.
Adv Immunol. 1994;57:1-127
PMID: 7872156
-
Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice.
Nature. 1996 Jan 25;379(6563):346-9
PMID: 8552190
-
Immunoglobulin G3 blocking antibodies to the fungal pathogen Cryptococcus neoformans.
J Exp Med. 1996 Apr 1;183(4):1905-9
PMID: 8666947
-
Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB.
Nature. 1996 Sep 19;383(6597):263-6
PMID: 8805703
-
Fc receptors.
Curr Opin Immunol. 1997 Feb;9(1):121-5
PMID: 9039776
-
Finally! The Brambell receptor (FcRB). Mediator of transmission of immunity and protection from catabolism for IgG.
Immunol Res. 1997 Feb;16(1):29-57
PMID: 9048207
-
Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling.
Cell. 1997 Jul 25;90(2):293-301
PMID: 9244303