Mj. Vanvugt et al., FCR GAMMA-CHAIN IS ESSENTIAL FOR BOTH SURFACE EXPRESSION AND FUNCTIONOF HUMAN FC-GAMMA-RI (CD64) IN-VIVO, Blood, 87(9), 1996, pp. 3593-3599
Most Ig receptors exist as hetero-oligomeric complexes with separate l
igand binding (alpha) and signal transducing (beta, gamma, or xi) subu
nits. For Fc gamma RIIIa and Fc epsilon RI, association with the FcR g
amma-chain is essential for surface expression. However, the human hig
h affinity IgG receptor, hFc gamma RI, was found to be surface-express
ed by itself in transient transfection models. We have now analyzed th
e integrity of hFc gamma RI expression in more detail in stable transf
ectants. In vitro we noted that, in the absence of FcR gamma-chain, su
rface expression of hFc gamma RI rapidly declined to background levels
, in both IIA1.6 B cells and NIH3T3 fibroblasts. The effect of FcR gam
ma-chain on hFc gamma RI surface expression in vivo was evaluated by u
sing two newly generated transgenic mouse lines, selectively expressin
g hFc gamma RI on myeloid cells. These transgenic mice were crossed wi
th FcR gamma-chain-deficient mice. Analysis of blood monocytes and per
itoneal macrophages showed that surface expression of hFc gamma RI was
reduced by similar to 80%. The remaining similar to 20% of receptors
were still capable of binding IgG-opsonized RBC, suggesting FcR gamma-
chain not to be critical for hFc gamma RI ligand-binding capacity. Imp
ortantly, however, hFc gamma RI signaling capacity was lost in FcR gam
ma-chain-deficient cells. No phagocytosis could be observed using eith
er ligand sensitized (EA-IgG2a) or CD64-targeted erythrocytes (using a
bispecific antibody) in both hFc gamma RI transgenic lines. This docu
ments the FcR gamma-chain to be indispensable for both surface membran
e expression and function of human Fc gamma RI in vivo. (C) 1996 by Th
e American Society of Hematology.