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Developmental extinction of major histocompatibility complex class II gene expression in plasmocytes is mediated by silencing of the transactivator gene CIITA

Silacci, P.
Mottet, A.
Published in Journal of Experimental Medicine. 1994, vol. 180, no. 4, p. 1329-1336
Abstract Constitutive major histocompatibility complex (MHC) class II gene expression is tightly restricted to antigen presenting cells and is under developmental control. Cells of the B cell lineage acquire the capacity to express MHC class II genes early during ontogeny and lose this property during terminal differentiation into plasma cells. Cell fusion experiments have suggested that the extinction of MHC class II expression in plasma cells is due to a dominant repression, but the underlying mechanisms are not understood. CIITA was recently identified as an MHC class II transactivator that is essential for MHC class II expression in B lymphocytes. We show here that inactivation of MHC class II genes in plasmocytes is associated with silencing of the CIITA gene. Moreover, experimentally induced expression of CIITA in plasmocytes leads to reexpression of MHC class II molecules to the same level as that observed on B lymphocytes. We therefore conclude that the loss of MHC class II expression observed upon terminal differentiation of B lymphocytes into plasmocytes results from silencing of the transactivator gene CIITA.
Keywords B-Lymphocytes/immunologyCell DifferentiationGene Expression RegulationGenes, MHC Class IIHumansPlasma Cells/ immunologyPlasmacytoma/geneticsPromoter Regions, GeneticProtein BindingTrans-Activators/ geneticsTumor Cells, Cultured
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PMID: 7931066
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