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Citations to this article

Antigen targeting to myeloid-specific human Fc gamma RI/CD64 triggers enhanced antibody responses in transgenic mice.
I A Heijnen, … , J S Verbeek, J G van de Winkel
I A Heijnen, … , J S Verbeek, J G van de Winkel
Published January 15, 1996
Citation Information: J Clin Invest. 1996;97(2):331-338. https://doi.org/10.1172/JCI118420.
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Antigen targeting to myeloid-specific human Fc gamma RI/CD64 triggers enhanced antibody responses in transgenic mice.

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Abstract

Besides their phagocytic effector functions, myeloid cells have an essential role as accessory cells in the induction of optimal humoral immune responses by presenting captured antigens and activating lymphocytes. Antigen presentation by human monocytes was recently found to be enhanced in vitro through the high-affinity Fc receptor for IgG (Fc gamma RI; CD64), which is exclusively present on myeloid cells. To evaluate a comparable role of Fc gamma RI in antigen presentation in vivo, we generated human Fc gamma RI transgenic mice. Under control of its endogenous promoter, human Fc gamma RI was selectively expressed on murine myeloid cells at physiological expression levels. As in humans, expression was properly regulated by the cytokines IFN-gamma, G-CSF, IL-4, and IL-10, and was up-regulated during inflammation. The human receptor expressed by murine macrophages bound monomeric human IgG and mediated particle phagocytosis and IgG complex internalization. To evaluate whether specific targeting of antigens to Fc gamma RI can induce enhanced antibody responses, mice were immunized with an anti-human Fc gamma RI antibody containing antigenic determinants. Transgenic mice produced antigen-specific antibody responses with high IgG1 titers and substantial IgG2a and IgG2b responses. These data demonstrate that human Fc gamma RI on myeloid cells is highly active in mediating enhanced antigen presentation in vivo, and show that anti-Fc gamma RI mAbs are promising vaccine adjuvants.

Authors

I A Heijnen, M J van Vugt, N A Fanger, R F Graziano, T P de Wit, F M Hofhuis, P M Guyre, P J Capel, J S Verbeek, J G van de Winkel

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M van Egmond, AJ van Vuuren, HC Morton, AB van Spriel, L Shen, FM Hofhuis, T Saito, TN Mayadas, JS Verbeek, JG van de Winkel
Blood 1999
The FcγRIa (CD64) Ligand Binding Chain Triggers Major Histocompatibility Complex Class II Antigen Presentation Independently of Its Associated FcR γ-Chain
MJ van Vugt, MJ Kleijmeer, T Keler, I Zeelenberg, MA van Dijk, JH Leusen, HJ Geuze, JG van de Winkel
Blood 1999
Interleukin-10 (IL-10) Selectively Enhances CIS3/SOCS3 mRNA Expression in Human Neutrophils: Evidence for an IL-10–Induced Pathway That Is Independent of STAT Protein Activation
MA Cassatella, S Gasperini, C Bovolenta, F Calzetti, M Vollebregt, P Scapini, M Marchi, R Suzuki, A Suzuki, A Yoshimura
Blood 1999
IFN-γ induces the high-affinity Fc receptor I for IgG (CD64) on human glomerular mesangial cells
P Uciechowski, M Schwarz, JE Gessner, RE Schmidt, K Resch, HH Radeke
European Journal of Immunology 1998
MUC1 cross-reactive Galα(l,3)Gal antibodies in humans switch immune responses from cellular to humoral
V Apostolopoulos, C Osinski, IF Mckenzie
Nature Medicine 1998
Regulation of murine hypersensitive responses by Fc receptors
T Takai, M Ono, A Ujike, T Yuasa
Allergology International 1998
The neutrophil: one of the cellular targets of interleukin-10
MA Cassatella
International Journal of Clinical & Laboratory Research 1998
Macrophage-targeted killing and vaccines
CA Guyre, MW Fanger
Research in Immunology 1998
The second and third extracellular domains of Fc γ RI (CD64) confer the unique high affinity binding of IgG2a
MD Hulett, PM Hogarth
Molecular Immunology 1998
The Immunoglobulin Receptors and their Physiological and Pathological Roles in Immunity
JG van de Winkel, PM Hogarth
1998
Fc Receptors as Targets for Immunotherapy
H Rouard, S Tamasdan, J Moncuit, S Moutel, J Michon, WH Fridman, JL Teillaud
International Reviews of Immunology 1997
Human IgG Fc Receptors
IA Heijnen, JG van de Winkel
International Reviews of Immunology 1997
Structural Bases of FcγR Functions
M Daéron
International Reviews of Immunology 1997
FcRECEPTOR BIOLOGY
M Daëron
Annual Review of Immunology 1997
Bispecific antibodies for the treatment of tumours and infectious diseases
DL Drakeman, MW Fanger, PK Wallace
Expert Opinion on Investigational Drugs 1997
Clinical significance of IgG Fc receptors and FcγR-directed immunotherapies
YM Deo, RF Graziano, R Repp, JG van de Winkel
Immunology Today 1997
Natural anti-Gal antibody as a universal augmenter of autologous tumor vaccine immunogenicity
U Galili, DC LaTemple
Immunology Today 1997
FcαRI (CD89) as a Novel Trigger Molecule for Bispecific Antibody Therapy
T Valerius, B Stockmeyer, AB van Spriel, RF Graziano, IE van den Herik-Oudijk, R Repp, YM Deo, J Lund, JR Kalden, M Gramatzki, JG van de Winkel
Blood 1997
F(c)gammaRI-targeted fusion proteins result in efficient presentation by human monocytes of antigenic and antagonist T cell epitopes
C Liu, J Goldstein, RF Graziano, J He, JK O'Shea, Y Deo, PM Guyre
Journal of Clinical Investigation 1996
Cell-Mediated Effects of Immunoglobulins
WH Fridman, C Sautès
1996

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