Functional block for 1α,25-dihydroxyvitamin D₃-mediated gene regulation in human B lymphocytes

Elements necessary for the steroid hormone 1α,25-dihydroxyvitamin D₃ (1α,25-(OH)₂D₃) to induce a biological response include the presence of specific intracellular receptors (vitamin D₃ receptors (VDR)) and modulation of gene expression via hormone-activated receptor binding to regulatory regions of target genes. These parameters were examined in normal and Epstein-Barr virus-immortalized human B cells and compared with 1α,25- (OH)₂D₃-responsive cells of the T and monocytic lineages. Although resting tonsillar B cells did not express VDR mRNA, activation of these cells with interleukin-4 induced VDR in the absence of exogenously supplemented 1α,25- (OH)₂D₃. As indicators of hormone-mediated gene regulation we analyzed modulation of CD23, a common B cell/monocyte surface antigen, and 24- hydroxylase. 1α,25-(OH)₂D₃ inhibited CD23 expression in U937 cells, yet failed to modulate CD23 expression in B cells. Furthermore, 1α,25-(OH)₂D₃ 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 findings suggest that although human B lymphocytes can express VDR mRNA and protein, they exhibit a functional block for vitamin D-dependent gene regulation.