Active suppression of major histocompatibility complex class II gene expression during differentiation from B cells to plasma cells.

Latron, F; Jotterand-Bellomo, M; Maffei, Antonella; Scarpellino, Léonardo; Bernard, Michel; Strominger, Jack L.; Accolla, Roberto S.

doi:10.1073/pnas.85.7.2229

Cited by 57 publications

(36 citation statements)

References 38 publications

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“…However, progression to the plasma B-cell stage after being stimulated with foreign antigens, various mitogens, and T-cell factors results in the uniform repression of the expression of all class II genes at the transcriptional level (46). NF-Y is associated with the protein cofactor PC4, which might play an important role in the NF-Y -mediated transcriptional control of the class II genes in B lymphocytes (47).…”

Section: Discussionmentioning

confidence: 99%

NF-Y–Dependent Cyclin B2 Expression in Colorectal Adenocarcinoma

Park¹,

Yu²,

Kim

et al. 2007

Clinical Cancer Research

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Purpose: Cyclin B2, a G 2 -M cyclin, is overexpressed in colorectal adenocarcinomas compared with the normal mucosa. This study examined the level of cyclin B2 overexpression according to the histologic findings and investigated the mechanism(s) and clinical implications of cyclin B2 overexpression in colorectal adenocarcinomas. Experimental Design: The immunoreactivity of the polyclonal antibodies to cyclin B2 was determined in colorectal cancer cells. The transcriptional regulation of cyclin B2 by NF-Y was analyzed using an in vitro transfection assay and an in vivo chromatin immunoprecipitation assay. The proliferative activity of the colorectal cancer cells in relation to cyclin B2 overexpression was further examined. Results: The cytoplasmic distribution of cyclin B2 immunoreactivity was positive in 42 of 65 (64.6%) cases of colorectal adenocarcinoma, and the level was similar regardless of the histologic type. A dominant-negative form of NF-YA effectively inhibited the cyclin B2 promoter activity, and NF-Y was found to bind three conserved CCAAT boxes in the cyclin B2 promoter in colorectal adenocarcinoma cells.Tumor cells with a higher functional cyclin B2 activity grew faster than those with a lower activity. Furthermore, there was a correlation between the cells showing immunoreactivity to cyclin B2 and those containing the proliferating cell nuclear antigen, a G 1 -S cyclin, which is also downstream of NF-Y in colorectal adenocarcinoma cells. Conclusions: Cyclin B2 seems to be a molecular marker of a colorectal adenocarcinoma and that its up-regulation and coordinate expression of the other cell cycle^related genes by NF-Y might contribute to tumor cell proliferation by accelerating cell cycle progression.Mitosis is induced by the activation of the M-phasepromoting factor, which is a protein kinase whose principal subunits are p34 cdc2 and cyclin B. Cyclin B is a regulatory subunit that varies in abundance throughout the cell cycle (1). The metaphase to anaphase transition marks the end of mitosis and is induced by the degradation of cyclin B, which in turn leads to the inactivation of M-phase -promoting factor. As the cell cycle progresses, cyclin B begins to accumulate when the cell enters the interphase, which is followed by the reactivation of M-phase -promoting factor and another round of mitosis. Therefore, the B-type cyclins are the primary mitotic cyclins, although several yeast B-type cyclins have been reported to function earlier in the cell cycle, particularly in the S phase (2, 3). There are two mammalian B-type cyclins, cyclins B1 and B2, which differ in their NH 2 termini but have 57% similarity (4 -6). Cyclins B1 and B2 are coexpressed in most dividing cells and, in association with cdc2, play a role in entering the G 2 -M phase, although their subcellular localization differs (7). Cyclin B1 is primarily cytoplasmic but constantly shuttles between the nucleus and the cytoplasm during the interphase. At the end of the prophase, cyclin B1 rapidly translocates to the nucleus (8, 9)...

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Section: Discussionmentioning

confidence: 99%

NF-Y–Dependent Cyclin B2 Expression in Colorectal Adenocarcinoma

Park¹,

Yu²,

Kim

et al. 2007

Clinical Cancer Research

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“…MHC class II gene transcription begins in the pre-B cell stage, is maintained until B-lymphocytes attain maturity (17,18), and is down-regulated when B-lymphocytes terminally differentiate into plasma cells (19,20). CIITA expression is also up-regulated in the pre-B cell stages and then lost upon terminal differentiation (21,22).…”

mentioning

confidence: 99%

A Novel Element and a TEF-2-like Element Activate the Major Histocompatibility Complex Class II Transactivator in B-lymphocytes

Ghosh

Piskurich

Wright

et al. 1999

Journal of Biological Chemistry

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Major histocompatibility complex (MHC) class II molecules play a central role in immune responses, and transcription of this family of genes requires the MHC class II transactivator (CIITA). CIITA has four promoters, which are transcribed in a tissue-specific manner. CIITA promoter III is constitutively active in mature B-lymphocytes. This report now describes the minimal 319-base pair promoter region necessary for maximal transcriptional activity in B-lymphocytes. Ultraviolet light and dimethylsulfate in vivo genomic footprinting analyses reveal five occupied DNA sequence elements present in intact B-lymphocytes. Functional analysis of these elements using promoter deletions and site-specific mutations demonstrates that at least two of the sites occupied in vivo are critical for transcriptional activity. In vitro protein/DNA analysis suggests that one of the sites is a TEF-2-like element and the other is occupied by a novel transcription activator. In addition, nuclear factor-1 associates with the promoter both in vivo and in vitro. In myeloma cell lines, loss of CIITA transcription correlates with a completely unoccupied CIITA promoter III. These findings suggest that CIITA transcription in B-lymphocytes is activated through at least two strong promoter elements, while loss of expression in myeloma cells is mediated through changes in promoter assembly.Major histocompatibility complex (MHC) 1 class II molecules play a fundamental role in presenting exogenous antigenic peptides to CD4 ϩ helper T lymphocytes (1). These activated CD4 ϩ T cells release stimulatory cytokines that augment the response of CD8 ϩ cytotoxic T lymphocytes (2). Constitutive expression of MHC class II molecules is restricted to professional antigen-presenting cells, such as B lymphocytes and dendritic cells, and can be induced by interferon-␥ (IFN-␥) in macrophages, endothelial cells, and fibroblasts (3, 4). The MHC class II family of genes are coordinately regulated at the level of transcription through a conserved trimeric promoter motif (3, 5). A major component of this transcription complex was cloned by genetic complementation of an in vitro mutagenized MHC class II negative B cell line, RJ2.2.5. This component was named the MHC class II transactivator (CIITA) and restored MHC class II cell surface expression in one subgroup of bare lymphocyte syndrome patient cells (6). CIITA has since been shown to be a key regulatory molecule in the expression of all the known genes involved in the MHC class II antigen-presenting pathway (6 -9). CIITA is required for constitutive expression of MHC class II on B-lymphocytes (10) and with a few exceptions, such as in respiratory epithelial cells and dendritic cells (11,12), is required for cytokine-induced expression in other cell types. Mice in which functional CIITA protein was ablated clearly demonstrated an absolute requirement for CI-ITA in B cell expression of MHC class II (13). It has been shown that the CIITA gene has four distinct promoters each transcribing a unique first exon, which are lo...

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“…In addition, endogenous CIITA mRNA expression has been shown to be completely suppressed in plasma B-cells, whereas unregulated overexpression of CIITA in plasma B-cells surprisingly restores MHC class II mRNA and protein expression to the elevated levels observed in mature B-cells (43). These results suggest active repression of CIITA expression accounts for the dominant suppressor plasma cell phenotype exhibited by mature B:plasma B-cell somatic cell hybrids (7,8), and further suggest CIITA plays an obligatory role in the normal tissue-specific regulation of MHC class II gene transcription.…”

mentioning

confidence: 82%

“…[3][4][5][6]. Additionally, in B lymphocytes MHC class II proteins are regulated in a stage-specific manner, as the high level of constitutive expression observed in mature B-cells is completely extinguished during progression to the plasma B-cell stage through repression at the transcriptional level (7,8).…”

mentioning

confidence: 99%

Biochemical Characterization of the NF-Y Transcription Factor Complex during B Lymphocyte Development

Ra¹

1998

Journal of Biological Chemistry

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Active suppression of major histocompatibility complex class II gene expression during differentiation from B cells to plasma cells.

Cited by 57 publications

References 38 publications

NF-Y–Dependent Cyclin B2 Expression in Colorectal Adenocarcinoma

NF-Y–Dependent Cyclin B2 Expression in Colorectal Adenocarcinoma

A Novel Element and a TEF-2-like Element Activate the Major Histocompatibility Complex Class II Transactivator in B-lymphocytes

Biochemical Characterization of the NF-Y Transcription Factor Complex during B Lymphocyte Development

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