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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 AhR mRNA expression in purified subpopulations of murine B cells. Microarray data were generated by Green et al. [1] from murine B cells sorted by flow cytometry based on B developmental stage-specific surface antigens. Expression levels of the AhR transcript within the listed differentiation stages was extracted from [1] and the corresponding distributions summarized and displayed as 'box-and-whiskers' plots (with the bottom and the top of the box corresponding to the first and third quartiles, the thick band inside the box indicating the median, and the end of the 'whiskers' extending to 1.5 times the interquartile range in both directions)
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Fig1: Relative AhR mRNA expression in purified subpopulations of murine B cells. Microarray data were generated by Green et al. [1] from murine B cells sorted by flow cytometry based on B developmental stage-specific surface antigens. Expression levels of the AhR transcript within the listed differentiation stages was extracted from [1] and the corresponding distributions summarized and displayed as 'box-and-whiskers' plots (with the bottom and the top of the box corresponding to the first and third quartiles, the thick band inside the box indicating the median, and the end of the 'whiskers' extending to 1.5 times the interquartile range in both directions)

Mentions: The study of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has come a long way. For many years, analysis of AhR function and activity was the purview solely of toxicologists interested in understanding how environmental chemicals are “sensed” by biological organisms. With regard to the immune system in particular, immunotoxicologists focused on a set of environmentally common, immunosuppressive chemicals including dioxins, most notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). These studies, in essence, exploited environmental chemicals as probes of biological systems to understand how the AhR functions and to begin to reveal for what purpose this evolutionarily conserved receptor/transcription factor exists. These studies were of enormous value since they provided a scaffold on which to build theories of the “nominal” function of the AhR. They also suggested that, at various points in B cell development and differentiation, B cells themselves, or stromal cells on which B cells depend for developmental signals, express AhR and serve as the immediate targets of endogenous or exogenous AhR ligands. Indeed, analysis of gene expression profiles in a panel of purified, developmentally defined normal murine B cells [1] demonstrates a hierarchy of AhR expression during B cell development (Fig. 1). Bone marrow pro- and pre-B cells express little or no AhR mRNA. In contrast, splenic transitional B cells, representing cells recently activated during clonal selection, have elevated AhR levels. Follicular, marginal zone, or germinal center B cells and plasmablasts express modest but variable AhR levels. Interestingly, plasma cells express high AhR levels, suggesting a role for the AhR in plasma cell development and/or function. This issue will be readdressed later in this manuscript.Fig. 1


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

Sherr DH, Monti S - Semin Immunopathol (2013)

Relative AhR mRNA expression in purified subpopulations of murine B cells. Microarray data were generated by Green et al. [1] from murine B cells sorted by flow cytometry based on B developmental stage-specific surface antigens. Expression levels of the AhR transcript within the listed differentiation stages was extracted from [1] and the corresponding distributions summarized and displayed as 'box-and-whiskers' plots (with the bottom and the top of the box corresponding to the first and third quartiles, the thick band inside the box indicating the median, and the end of the 'whiskers' extending to 1.5 times the interquartile range in both directions)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Relative AhR mRNA expression in purified subpopulations of murine B cells. Microarray data were generated by Green et al. [1] from murine B cells sorted by flow cytometry based on B developmental stage-specific surface antigens. Expression levels of the AhR transcript within the listed differentiation stages was extracted from [1] and the corresponding distributions summarized and displayed as 'box-and-whiskers' plots (with the bottom and the top of the box corresponding to the first and third quartiles, the thick band inside the box indicating the median, and the end of the 'whiskers' extending to 1.5 times the interquartile range in both directions)
Mentions: The study of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has come a long way. For many years, analysis of AhR function and activity was the purview solely of toxicologists interested in understanding how environmental chemicals are “sensed” by biological organisms. With regard to the immune system in particular, immunotoxicologists focused on a set of environmentally common, immunosuppressive chemicals including dioxins, most notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). These studies, in essence, exploited environmental chemicals as probes of biological systems to understand how the AhR functions and to begin to reveal for what purpose this evolutionarily conserved receptor/transcription factor exists. These studies were of enormous value since they provided a scaffold on which to build theories of the “nominal” function of the AhR. They also suggested that, at various points in B cell development and differentiation, B cells themselves, or stromal cells on which B cells depend for developmental signals, express AhR and serve as the immediate targets of endogenous or exogenous AhR ligands. Indeed, analysis of gene expression profiles in a panel of purified, developmentally defined normal murine B cells [1] demonstrates a hierarchy of AhR expression during B cell development (Fig. 1). Bone marrow pro- and pre-B cells express little or no AhR mRNA. In contrast, splenic transitional B cells, representing cells recently activated during clonal selection, have elevated AhR levels. Follicular, marginal zone, or germinal center B cells and plasmablasts express modest but variable AhR levels. Interestingly, plasma cells express high AhR levels, suggesting a role for the AhR in plasma cell development and/or function. This issue will be readdressed later in this manuscript.Fig. 1

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