Regulation of human β2-microglobulin transactivation in hematopoietic cells

beta(2)-Microglobulin (beta(2)m) is a chaperone of major histocompatibility complex (MHC) class I (-like) molecules that play a central role in antigen presentation, immunoglobulin transport, and iron metabolism. It is therefore of importance that beta(2)m is adequately expressed in cells that perform these functions, such as hematopoietic cells. In this study, we investigated the transcriptional regulation of beta(2)m in lymphoid and myeloid cell lines through a promoter containing a putative E box, Ets/interferon-stimulated response element (ISRE), and kappa B site. Here we show that upstream stimulatory factor 1 (USF1) and USF2 bind to the E box and regulate beta(2)m transactivation. The nuclear factor kappa B (NF-kappa B) subunits p50 and p65 bind to the kappa B box and p65 transactivates beta(2)m. Interferon regulatory factor 1 (IRF1), IRF2, IRF4, and IRF8, but not PU.1, bind to the Ets/ISRE, and IRF1 and IRF3 are strong transactivators of beta(2)m. Together, all 3 boxes are important for the constitutive and cytokine-induced levels of beta(2)m expression in lymphoid and myeloid cell types. As such, beta(2)m transactivation is under the control of important transcriptional pathways, which are activated during injury, infection, and inflammation.