The immunogenicity of L1210 lymphoma clones correlates with their ability to function as antigen-presenting cells.

Major histocompatibility complex class II (MHCII) antigen expression is directly correlated with immunogenicity, and inversely correlated with tumorigenicity, in clones of the L1210 murine B lymphoma. Moreover, loss of MHCII expression on human diffuse large B-cell lymphoma is associated with dramatic decreases in patient survival. Thus, the role that MHCII antigens play in the progression of B-cell lymphomas is clinically important.

Histone deacetylases inhibit IFN-gamma-inducible gene expression in mouse trophoblast cells.

Trophoblast cells are the first cells to differentiate from the developing mammalian embryo, and they subsequently form the blastocyst-derived component of the placenta. IFN-gamma plays critical roles in activating innate and adaptive immunity, as well as apoptosis. In mice, IFN-gamma is produced in the pregnant uterus, and is essential for formation of the decidual layer of the placenta and remodeling of the uterine vasculature.

Dampening of IFN-gamma-inducible gene expression in human choriocarcinoma cells is due to phosphatase-mediated inhibition of the JAK/STAT-1 pathway.

Trophoblast cells (TBCs) form the blastocyst-derived component of the placenta and play essential roles in fetal maintenance. The proinflammatory cytokine IFN-gamma plays a central role in activating cellular immunity, controlling cell proliferation, and inducing apoptosis. IFN-gamma is secreted by uterine NK cells in the placenta during pregnancy and in mice is required for proper formation of the decidual layer and remodeling of the uterine vasculature.

Regulation of major histocompatibility complex class II gene expression in trophoblast cells.

Trophoblast cells are unique because they are one of the few mammalian cell types that do not express major histocompatibility complex (MHC) class II antigens, either constitutively or after exposure to IFN-gamma. The absence of MHC class II antigen expression on trophoblast cells has been postulated to be one of the essential mechanisms by which the semi-allogeneic fetus evades immune rejection reactions by the maternal immune system. Consistent with this hypothesis, trophoblast cells from the placentas of women suffering from chronic inflammation of unknown etiology and spontaneous recurrent miscarriages have been reported to aberrantly express MHC class II antigens.

Class II transactivator (CIITA) promoter methylation does not correlate with silencing of CIITA transcription in trophoblasts.

Trophoblast cells are unique because they do not express major histocompatibility complex (MHC) class II antigens, either constitutively or after exposure to interferon-gamma (IFN-gamma). The absence of MHC class II antigens on trophoblasts is thought to play a critical role in preventing rejection of the fetus by the maternal immune system. The inability of trophoblasts to express MHC class II genes is primarily due to lack of the class II transactivator (CIITA), a transacting factor that is required for constitutive and IFN-gamma-inducible MHC class II transcription.

DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.

MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and directly correlated with immunogenicity in clones of the mouse L1210 lymphoma (1 ). Understanding the mechanisms by which class II Ag expression is regulated in L1210 lymphoma may facilitate the development of immunotherapeutic approaches for the treatment of some types of lymphoma and leukemia. This study demonstrates that the variation in MHC class II Ag expression among clones of L1210 lymphoma is due to differences in the expression of the class II transactivator (CIITA).