Regulation of Fc epsilonRI expression on human monocytic cells by ligand and IL-4.

Background: The Fc epsilonRI subunit composition and kinetic of expression differ between antigen-presenting cells and mast cells. Up to now, there has been no human in vitro model available that mimics the characteristics on monocytes.

Objective: The characterization of a natural human monocytic cell line (THP1), which expresses Fc epsilonRI, and the comparison to primary human monocytes and other monocytic cell lines, which only express Fc epsilonRI after transfection with the human Fc epsilonRI alpha-chain gene.

Cooperation of binding sites for STAT6 and NF kappa B/rel in the IL-4-induced up-regulation of the human IgE germline promoter.

Ig heavy chain class switching is directed by cytokines inducing transcription from unrearranged CH genes. Subsequently, such primed cells can undergo switch recombination to express the selected new isotype. In the case of IgE class switching, IL-4 activates the IgE germline promoter by inducing the interaction of the transcription factor STAT6 (IL-4STAT) with a responsive DNA element in the proximal region of the promoter.

The transcription factor B-cell-specific activator protein is not involved in the IL-4-induced activation of the human IgE germline promoter.

Transcriptional activity of the human IgE germline gene is a prerequisite for a subsequent deletional rearrangement of the Ig heavy-chain locus, the hallmark of isotype switching to IgE. The B-cell-specific transcription factor B cell-specific activator protein (BSAP) was described for being critically involved in the IL-4 up-regulation of the murine IgE germline gene. Our study was initiated to evaluate the regulatory role of BSAP in the human IgE germline promoter.