INTERFERON-ALPHA INDUCES THE EXPRESSION OF THE L-SELECTIN HOMING RECEPTOR IN HUMAN B-LYMPHOID CELLS

The L-selectin homing receptor expressed by lymphocytes mediates the i nitial attachment of these cells to high endothelial venules within pe ripheral lymph nodes. This adhesive interaction is required for the mi gration of B and T lymphocytes from the blood into peripheral lymph no des. There is currently little information regarding the nature of the factors involved in the regulation of the synthesis and expression of L-selectin by lymphocytes. In this report, the immunomodulatory cytok ine interferon-alpha (IFN-alpha) was shown to markedly upregulate the surface density of L-selectin in the established human B lymphoid Daud i cell line and in a subpopulation of tissue-derived human B lymphoid cells. Other cytokines such as EFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-2, IL-4, IL-6, and low molecular weight B cell growth factor did not affect L-selectin surface expression in the model Daudi B cell line. Upregulation of L-selectin surface density i n IFN-alpha-treated Daudi B cells correlated directly with an increase in L-selectin mRNA steady state levels and enhanced L-select-independ ent binding to a carbohydrate-based ligand, phosphomonoester core poly saccharide. Regulation of L-selectin mRNA by EFN-alpha had characteris tics similar to that of classical IFN-stimulated genes including rapid kinetics of induction, protein-synthesis-independent induction, and s ensitivity to tyrosine-kinase inhibitors. IFN-alpha did not upregulate L-selectin mRNA levels or surface expression in an IFN-resistant Daud i subclone which exhibits a defect in the signal transduction pathway required for the transcriptional induction of IFN-stimulated genes. Th ese data demonstrate a fundamental role for IFN-alpha in regulating L- selectin synthesis and expression in human B lymphoid cells and sugges t a mechanism whereby this cytokine regulates the regional trafficking of B cells to peripheral lymph nodes.