Regulation of human β2-microglobulin transactivation in hematopoietic cells

Abstract

Abstract β2-Microglobulin (β2m) 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 β2m is adequately expressed in cells that perform these functions, such as hematopoietic cells. In this study, we investigated the transcriptional regulation of β2m in lymphoid and myeloid cell lines through a promoter containing a putative E box, Ets/interferon-stimulated response element (ISRE), and κB site. Here we show that upstream stimulatory factor 1 (USF1) and USF2 bind to the E box and regulate β2m transactivation. The nuclear factor κB (NF-κB) subunits p50 and p65 bind to the κB box and p65 transactivates β2m. 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 β2m. Together, all 3 boxes are important for the constitutive and cytokine-induced levels of β2m expression in lymphoid and myeloid cell types. As such, β2m transactivation is under the control of important transcriptional pathways, which are activated during injury, infection, and inflammation.