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The role of the aryl hydrocarbon receptor in normal and malignant B cell development.

Sherr DH, Monti S - Semin Immunopathol (2013)

Bottom Line: Other articles in this edition summarize AhR function during T cell and antigen-presenting cell development and function, including the effects of AhR activation on dendritic cell function, T cell skewing, inflammation, and autoimmune disease.Here, we focus on AhR expression and function during B cell differentiation.Finally, a putative role for the AhR in the basic biology of B cell malignancies, many of which have been associated with exposure to environmental AhR ligands, is discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Health, Boston University School of Public Health, 72 East Concord Street (R-408), Boston, MA, 02118, USA, dsherr@bu.edu.

ABSTRACT
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically studied for its role in environmental chemical-mediated toxicity and carcinogenicity. In the last 5 years, however, it has become clear that the AhR, presumably activated by endogenous ligand(s), plays an important role in immune system development and function. Other articles in this edition summarize AhR function during T cell and antigen-presenting cell development and function, including the effects of AhR activation on dendritic cell function, T cell skewing, inflammation, and autoimmune disease. Here, we focus on AhR expression and function during B cell differentiation. Studies exploiting immunosuppressive environmental chemicals to probe the role of the AhR in humoral immunity are also reviewed to illustrate the multiple levels at which a "nominally activated" AhR could control B cell differentiation from the hematopoietic stem cell through the pro-B cell, mature B cell, and antibody-secreting plasma cell stages. Finally, a putative role for the AhR in the basic biology of B cell malignancies, many of which have been associated with exposure to environmental AhR ligands, is discussed.

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Relative expression of AhR mRNA and AhR target genes in human tumor cell lines. Analysis of microarray data obtained from 1,036 human cancer cell lines (http://www.broadinstitute.org/ccle/home) is presented. a Data corresponding to the five lymphoid malignancies listed and five transcripts, including AhR and four of its putative targets, are displayed as a color-coded gene-by-sample heat map, with rows (genes) and columns (samples) sorted by hierarchical clustering [136]. b Microarray data for the same five lymphoid cancers were analyzed, and genes ranked by Pearson correlation between the level of AhR expression and that of four known AhR target genes, CYP1B1, NQO1, TIPARP, and AhRR. Permutation-based p values and the corresponding FDR-corrected q values are shown. c A Kolmogorov–Smirnov test was performed to assess the strength of the association between AhR and its four targets. The x-axis lists the genes in the human transcriptome sorted by their distance from AhR (from the closest, left, to the furthest, right). The position of the four AhR targets (red ticks) is significantly skewed toward the left-hand side of the list (permutation-based p value = 0.021) [137]
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Fig4: Relative expression of AhR mRNA and AhR target genes in human tumor cell lines. Analysis of microarray data obtained from 1,036 human cancer cell lines (http://www.broadinstitute.org/ccle/home) is presented. a Data corresponding to the five lymphoid malignancies listed and five transcripts, including AhR and four of its putative targets, are displayed as a color-coded gene-by-sample heat map, with rows (genes) and columns (samples) sorted by hierarchical clustering [136]. b Microarray data for the same five lymphoid cancers were analyzed, and genes ranked by Pearson correlation between the level of AhR expression and that of four known AhR target genes, CYP1B1, NQO1, TIPARP, and AhRR. Permutation-based p values and the corresponding FDR-corrected q values are shown. c A Kolmogorov–Smirnov test was performed to assess the strength of the association between AhR and its four targets. The x-axis lists the genes in the human transcriptome sorted by their distance from AhR (from the closest, left, to the furthest, right). The position of the four AhR targets (red ticks) is significantly skewed toward the left-hand side of the list (permutation-based p value = 0.021) [137]

Mentions: Microarray analysis of 1,036 human cancer cell lines generated at the Broad Institute, i.e., the Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home) (Fig. 3), revealed a hierarchy of AhR expression in which low levels of AhR were expressed in diffuse large B cell lymphomas, unspecified B cell lymphomas, and myelomas and notably higher levels in Hodgkin’s lymphomas and chronic lymphocytic leukemias (Fig. 4). Interestingly, expression of three (CYP1B1, TIPARP, and AhRR) of four (CYP1B1, TIPARP, AhRR, and NQO1) well-established AhR target genes chosen at random appear to track with AhR expression in the B lineage cancer subtypes, suggesting, but not proving, constitutive AhR activity in these tumor lines as previously documented in other tumor types [50, 82, 120–126].Fig. 4


The role of the aryl hydrocarbon receptor in normal and malignant B cell development.

Sherr DH, Monti S - Semin Immunopathol (2013)

Relative expression of AhR mRNA and AhR target genes in human tumor cell lines. Analysis of microarray data obtained from 1,036 human cancer cell lines (http://www.broadinstitute.org/ccle/home) is presented. a Data corresponding to the five lymphoid malignancies listed and five transcripts, including AhR and four of its putative targets, are displayed as a color-coded gene-by-sample heat map, with rows (genes) and columns (samples) sorted by hierarchical clustering [136]. b Microarray data for the same five lymphoid cancers were analyzed, and genes ranked by Pearson correlation between the level of AhR expression and that of four known AhR target genes, CYP1B1, NQO1, TIPARP, and AhRR. Permutation-based p values and the corresponding FDR-corrected q values are shown. c A Kolmogorov–Smirnov test was performed to assess the strength of the association between AhR and its four targets. The x-axis lists the genes in the human transcriptome sorted by their distance from AhR (from the closest, left, to the furthest, right). The position of the four AhR targets (red ticks) is significantly skewed toward the left-hand side of the list (permutation-based p value = 0.021) [137]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824572&req=5

Fig4: Relative expression of AhR mRNA and AhR target genes in human tumor cell lines. Analysis of microarray data obtained from 1,036 human cancer cell lines (http://www.broadinstitute.org/ccle/home) is presented. a Data corresponding to the five lymphoid malignancies listed and five transcripts, including AhR and four of its putative targets, are displayed as a color-coded gene-by-sample heat map, with rows (genes) and columns (samples) sorted by hierarchical clustering [136]. b Microarray data for the same five lymphoid cancers were analyzed, and genes ranked by Pearson correlation between the level of AhR expression and that of four known AhR target genes, CYP1B1, NQO1, TIPARP, and AhRR. Permutation-based p values and the corresponding FDR-corrected q values are shown. c A Kolmogorov–Smirnov test was performed to assess the strength of the association between AhR and its four targets. The x-axis lists the genes in the human transcriptome sorted by their distance from AhR (from the closest, left, to the furthest, right). The position of the four AhR targets (red ticks) is significantly skewed toward the left-hand side of the list (permutation-based p value = 0.021) [137]
Mentions: Microarray analysis of 1,036 human cancer cell lines generated at the Broad Institute, i.e., the Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home) (Fig. 3), revealed a hierarchy of AhR expression in which low levels of AhR were expressed in diffuse large B cell lymphomas, unspecified B cell lymphomas, and myelomas and notably higher levels in Hodgkin’s lymphomas and chronic lymphocytic leukemias (Fig. 4). Interestingly, expression of three (CYP1B1, TIPARP, and AhRR) of four (CYP1B1, TIPARP, AhRR, and NQO1) well-established AhR target genes chosen at random appear to track with AhR expression in the B lineage cancer subtypes, suggesting, but not proving, constitutive AhR activity in these tumor lines as previously documented in other tumor types [50, 82, 120–126].Fig. 4

Bottom Line: Other articles in this edition summarize AhR function during T cell and antigen-presenting cell development and function, including the effects of AhR activation on dendritic cell function, T cell skewing, inflammation, and autoimmune disease.Here, we focus on AhR expression and function during B cell differentiation.Finally, a putative role for the AhR in the basic biology of B cell malignancies, many of which have been associated with exposure to environmental AhR ligands, is discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Health, Boston University School of Public Health, 72 East Concord Street (R-408), Boston, MA, 02118, USA, dsherr@bu.edu.

ABSTRACT
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically studied for its role in environmental chemical-mediated toxicity and carcinogenicity. In the last 5 years, however, it has become clear that the AhR, presumably activated by endogenous ligand(s), plays an important role in immune system development and function. Other articles in this edition summarize AhR function during T cell and antigen-presenting cell development and function, including the effects of AhR activation on dendritic cell function, T cell skewing, inflammation, and autoimmune disease. Here, we focus on AhR expression and function during B cell differentiation. Studies exploiting immunosuppressive environmental chemicals to probe the role of the AhR in humoral immunity are also reviewed to illustrate the multiple levels at which a "nominally activated" AhR could control B cell differentiation from the hematopoietic stem cell through the pro-B cell, mature B cell, and antibody-secreting plasma cell stages. Finally, a putative role for the AhR in the basic biology of B cell malignancies, many of which have been associated with exposure to environmental AhR ligands, is discussed.

Show MeSH
Related in: MedlinePlus