FUNCTIONAL BLOCK FOR 1-ALPHA,25-DIHYDROXYVITAMIN D-3-MEDIATED GENE-REGULATION IN HUMAN B-LYMPHOCYTES

Elements necessary for the steroid hormone 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25-(OH)(2)D-3) to induce a biological response include t he presence of specific intracellular receptors (vitamin D-3 receptors (VDR)) and modulation of gene expression via hormone-activated recept or binding to regulatory regions of target genes. These parameters wer e examined in normal and Epstein-Barr virus-immortalized human B cells and compared with 1 alpha,25-(OH)(2)D-3-responsive cells of the T and monocytic lineages. Although resting tonsillar B cells did not expres s VDR mRNA, activation of these cells with interleukin-4 induced VDR i n the absence of exogenously supplemented 1 alpha,25-(OH)(2)D-3. As in dicators of hormone-mediated gene regulation we analyzed modulation of CD23, a common B cell/monocyte surface antigen, and 28-hydroxylase. 1 alpha,25-(OH)(2)D-3 inhibited CD23 expression in U937 cells, yet fail ed to modulate CD23 expression in B cells. Furthermore, 1 alpha,25-(OH )(2)D-3 induced 24-hydroxylase mRNA expression and metabolic activity in both U937 cells and lectin-activated T cells, yet failed to induce 24-hydroxylase mRNA or its metabolic activity in B cells. These findin gs suggest that although human B lymphocytes can express VDR mRNA and protein, they exhibit a functional block for vitamin D dependent gene regulation.