FCR GAMMA-CHAIN IS ESSENTIAL FOR BOTH SURFACE EXPRESSION AND FUNCTIONOF HUMAN FC-GAMMA-RI (CD64) IN-VIVO

Citation
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
Citations number
35
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
87
Issue
9
Year of publication
1996
Pages
3593 - 3599
Database
ISI
SICI code
0006-4971(1996)87:9<3593:FGIEFB>2.0.ZU;2-X
Abstract
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.