FcgammaRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses, and protection from bacterial infection.
The high-affinity receptor for IgG, FcgammaRI, shares its capacity to bind IgG2a immune complexes (IgG2a-IC) with the low-affinity receptor FcgammaRIII and complement factors, hampering the definition of its biological role. Moreover, in vivo, FcgammaRI is occupied by monomeric IgG2a, reducing its accessibility to newly formed IgG2a-IC. By using a variety of FcgammaR(-/-) mice, we demonstrate that in the absence of FcgammaRI, the IgG2a-IC-induced cellular processes of phagocytosis, cytokine release, cellular cytotoxicity, and antigen presentation are impaired. FcgammaRI(-/-) mice showed impaired hypersensitivity responses, strongly reduced cartilage destruction in an arthritis model, and impaired protection from a bacterial infection. We conclude that FcgammaRI contributes substantially to a variety of IgG2a-IC-dependent immune functions and immunopathological responses.
Ioan-Facsinay
A
A
Department of Human Genetics, Leiden University Medical Center, 2333 AL Leiden, The Netherlands.
de Kimpe
S J
SJ
Hellwig
S M M
SM
van Lent
P L
PL
Hofhuis
F M A
FM
van Ojik
H H
HH
Sedlik
C
C
da Silveira
S A
SA
Gerber
J
J
de Jong
Y F
YF
Roozendaal
R
R
Aarden
L A
LA
van den Berg
W B
WB
Saito
T
T
Mosser
D
D
Amigorena
S
S
Izui
S
S
van Ommen
G J B
GJ
van Vugt
M
M
van de Winkel
J G J
JG
Verbeek
J S
JS
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001886:Bordetella pertussis / Q000276:immunology*; D002356:Cartilage / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D007109:Immunity / Q000235:genetics; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D014917:Whooping Cough / Q000276:immunology*
D007074:Immunoglobulin G; D017452:Receptors, IgG