BLIMP-I mediates extinction of major histocompatibility class II transactivator expression in plasma cells.
Class II transactivator (CIITA), a coactivator required for class II major histocompatibility complex (MHC) transcription, is expressed in B cells but extinguished in plasma cells. This report identifies B lymphocyte-induced maturation protein I (BLIMP-I), a transcriptional repressor that is capable of triggering plasma cell differentiation, as a developmentally regulated repressor of CIITA transcription. BLIMP-I represses the B cell-specific promoter of the human gene that encodes CIITA (MHC2TA) in a binding site-dependent manner. Decreased CIITA correlates with increased BLIMP-I during plasma cell differentiation in cultured cells. Ectopic expression of BLIMP-I represses endogenous mRNA for CIITA and the CIITA targets, class II MHC, invariant chain and H2-DM (the murine equivalent of HLA-DM) in primary splenic B cells as well as 18-81 pre-B cells. Thus, the BLIMP-I program of B cell differentiation includes loss of antigen presentation via extinction of CIITA expression.
Piskurich
J F
JF
Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lin
K I
KI
Lin
Y
Y
Wang
Y
Y
Ting
J P
JP
Calame
K
K
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059805:HLA-DR alpha-Chains; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C087042:PRDM1 protein, human; D004247:DNA; D000074462:Positive Regulatory Domain I-Binding Factor 1