Fcγ receptor IIb strongly regulates Fcγ receptor-facilitated T cell activation by dendritic cells.

J Immunol 2012 Jul 30;189(1):92-101. Epub 2012 May 30.

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.

FcγR ligation by Ag-Ab immune complexes (IC) not only mediates effective Ag uptake, but also strongly initiates dendritic cell (DC) maturation, a requirement for effective T cell activation. Besides the activating FcγRI, FcγRIII, and FcγRIV, the inhibitory FcγRIIb is expressed on DCs. It is unclear how the ratio between signals from the activating FcγR and the inhibitory FcγRIIb determines the outcome of FcγR ligation on DCs. By microarray analysis, we compared the transcriptomes of steady state and IC-activated bone marrow-derived wild-type (WT) DCs expressing all FcγR or DCs expressing only activating FcγR (FcγRIIb knockout [KO]) or only the inhibitory FcγRIIb (FcR γ-chain KO). In WT DCs, we observed a gene expression profile associated with effective T cell activation, which was absent in FcR γ-chain KO, but strikingly more pronounced in FcγRIIb KO bone marrow-derived DCs. These microarray results, confirmed at the protein level for many cytokines and other immunological relevant genes, demonstrate that the transcriptome of IC-activated DCs is dependent on the presence of the activating FcγR and that the modulation of the expression of the majority of the genes was strongly regulated by FcγRIIb. Our data suggest that FcγRIIb-deficient DCs have an improved capacity to activate naive T lymphocytes. This was confirmed by their enhanced FcγR-dependent Ag presentation and in vivo induction of CD8(+) T cell expansion compared with WT DCs. Our findings underscore the potency of FcγR ligation on DCs for the effective induction of T cell immunity by ICs and the strong regulatory role of FcγRIIb.

Download full-text PDF

Source
http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.1103703
Publisher Site
http://dx.doi.org/10.4049/jimmunol.1103703DOI Listing
July 2012
35 Reads

Publication Analysis

Top Keywords

inhibitory fcγriib
12
activating fcγr
12
fcγr ligation
12
cell activation
12
dcs
10
effective cell
8
ligation dcs
8
dcs expressing
8
bone marrow-derived
8
dcs microarray
8
fcr γ-chain
8
fcγr
7
fcγriib
7
cell
6
fcγr dcs
4
expressing fcγr
4
fcγ receptor
4
marrow-derived wild-type
4
wild-type dcs
4
fcγriib data
4

Similar Publications