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Differential Gene Expression Modulated by the Cytoplasmic Domain of FcRIa (CD64) -Chain¹

Hongwei Qin^*, Jeffrey C. Edberg^*, Andrew W. Gibson^*, Grier P. Page, Lihong Teng^* and Robert P. Kimberly^2,*

^* Department of Medicine, and Section on Statistical Genetics, Department of Biostatistics, University of Alabama, Birmingham, AL 35294

The cytoplasmic domain (CY) of the ligand-binding -chain of the -chain-associated FcRs can modulate receptor function such as phagocytosis, endocytosis, and intracellular trafficking of receptor-Ag complexes. To assess the potential role of the CY domain of human FcRIa (CD64) -chain in the transcriptional regulation of receptor-induced gene expression, we developed stably transfected murine macrophage cell lines expressing a full-length or a CY deletion mutant (tail-less) of human FcRIa to analyze gene expression in response to receptor-specific cross-linking. Using the Affymetrix murine genome U74Av2 GeneChip array, we observed >100 candidate genes having 2-fold difference expression at 1.5 and 3 h after stimulation. Focusing on several immunologically related genes, we confirmed differential expression of M-CSF, macrophage inhibitory cytokine-1, leukocyte-specific protein 1, MIP-2, and IL-1R antagonist by RT-PCR and RNase protection assays. Analysis of mRNA stability indicated that the differential regulation of gene expression by the CY of the CD64 -chain is at the level of gene transcription. Our results indicate that the CY of the CD64 -chain modulates transcriptional activity induced by receptor-specific engagement in macrophages and provides a framework for understanding distinct expression profiles elicited by different Fc -chain-associated receptors.

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