PRB is required for interferon-gamma-induction of the MHC class II A beta gene

PRE is required for IFN-gamma-induction of MHC class II in human tumor cell lines, providing a potential link between tumor suppressors and the immune system. However, other genes, such as cyclin D1, show pRB-dependency only in tumor cells, so by analogy, pRB may not be necessary for cII-regulation in normal cells. Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB+/+ mouse embryonic fibroblasts (MEFs), but deficient in RB-/- MEFs, Inducibility is restored in RB-/- MEFs stably transfected with wild type RE cDNA or infected with an adenovirus expressin g pRB. Thus, involvement of pRB in MHC class II expression is conserved in the mouse and is not an aberrant feature of tumorigenic, aneuploid, human t umor cells. Although cII genes are generally induced in a coordinate fashio n, suggesting a common mechanism, we found that pRB was specifically requir ed for induction of the A beta, but not A alpha or other MHC cII genes incl uding E beta, Ii and H2-M alpha. Finally, IFN-gamma-induction of class II t ransactivator (CIITA), was pRB-independent, suggesting that pRB works downs tream of this master-regulator of MHC class II expression.