title: Effects of AhR ligands on the production of immunoglobulins in purified mouse B cells.
abstract: The aryl hydrocarbon receptor (AhR) has been shown to play important roles in the immune system, and contributions of AhR ligands to the differentiation and functions of Th17/Treg cells have recently been established. However, it has not been fully clarified whether AhR plays roles in B cell differentiation and functions. The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly potent AhR agonist, was reported to suppress the production of immunoglobulin M (IgM) in a transformed mouse B cell line. However, TCDD exhibits high toxicity toward cells and has unknown activities except for its action as an AhR agonist. In the present study, we tried to clarify how an endogenously generated AhR agonist affects mouse B cell differentiation and functions in terms of the direct effects on the expression of Ig subclasses in purified mouse B cells stimulated with an anti-CD40 antibody and interleukin-4. The AhR agonist 2-(1'H-indole-3'- carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), which is derived via tryptophan metabolism, suppressed the expression of not only IgM, but also IgG1 and IgE. ITE was also found to suppress the expression of secreted-type Ig mRNAs and plasma cell-specific genes. These findings indicate that the endogenous AhR agonist suppresses B cell differentiation into Ig-secreting plasma cells.
authors.affiliation: Pharmaceutical Frontier Research Laboratories of Central Pharmaceutical Research Institute, Japan Tobacco, 1-13-2 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ken
authors.initials: K
authors.lastname: Katsuya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oka
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Koizumi
authors.forename: Daiko
authors.initials: D
authors.lastname: Wakita
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kitamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D017578:Immunoglobulin Class Switching; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics; D007211:Indoles / Q000494:pharmacology*; D015847:Interleukin-4 / Q000502:physiology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism
chemical_list: C548651:2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester; C511621:2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide; D001391:Azo Compounds; D007136:Immunoglobulins; D007211:Indoles; D008024:Ligands; D011720:Pyrazoles; D018336:Receptors, Aryl Hydrocarbon; D013844:Thiazoles; D014157:Transcription Factors; D015847:Interleukin-4; D019363:Cytochrome P-450 CYP1A1; D011503:Transglutaminases