Piskurich J F, Lin K I, Lin Y, Wang Y, Ting J P, Calame K
Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Nat Immunol. 2000 Dec;1(6):526-32. doi: 10.1038/82788.
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.
II类反式激活因子（CIITA）是II类主要组织相容性复合体（MHC）转录所需的一种共激活因子，在B细胞中表达，但在浆细胞中消失。本报告鉴定出B淋巴细胞诱导成熟蛋白I（BLIMP-I），一种能够触发浆细胞分化的转录抑制因子，是CIITA转录的发育调控抑制因子。BLIMP-I以结合位点依赖的方式抑制编码CIITA（MHC2TA）的人类基因的B细胞特异性启动子。在培养细胞的浆细胞分化过程中，CIITA的减少与BLIMP-I的增加相关。BLIMP-I的异位表达抑制了原代脾B细胞以及18-81前B细胞中CIITA的内源性mRNA以及CIITA的靶标II类MHC、恒定链和H2-DM（小鼠等同物HLA-DM）。因此，B细胞分化的BLIMP-I程序包括通过CIITA表达的消失而丧失抗原呈递。
