Skip Navigation



ToxSci Advance Access published online on May 28, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg132
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
74/2/315    most recent
kfg132v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Inouye, K.
Right arrow Articles by Nohara, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Inouye, K.
Right arrow Articles by Nohara, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received January 22, 2003; accepted April 23, 2003
© 2003 Society of Toxicology

Immunotoxicology

Suppressive Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on the High-Affinity Antibody Response in C57BL/6 Mice

Kaoru Inouye 1, Tomohiro Ito 2, Hidekazu Fujimaki 2, Yoshimasa Takahashi 3, Toshitada Takemori 3, Xiaoqing Pan 2, Chiharu Tohyama 2, Keiko Nohara 2*

1 Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan; Domestic Research Fellow, Japan Society for the Promotion of Science, Tokyo 102-0083, Japan
2 Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan; CREST, Japan Science and Technology, Kawaguchi 332-0012, Japan
3 Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-0044, Japan

* To whom correspondence should be addressed. E-mail: keikon{at}nies.go.jp.


  Abstract

In the humoral immune response to invasion of foreign antigens, B cells differentiate into low-affinity antibody-forming cells (AFCs) that mainly secrete IgM, or, through germinal center (GC) formation, into high-affinity AFCs that secrete IgG class antibodies with a higher affinity for the antigen. Previous studies have established the suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on low-affinity antibody responses to antigens. However, whether and how TCDD affects the high-affinity antibody response to antigens has not yet been clarified. In the present study, we investigated the effects of TCDD on GC formation, high-affinity AFC generation, and high-affinity antibody production in the primary humoral immune response. C57BL/6 mice were orally administered 0 or 20 µg/kg of TCDD and subsequently immunized with alum-precipitated ovalbumin (OVA) on Day 0, and then, GC formation in the spleen and OVA-specific antibodies in the plasma were evaluated until Day 14 postimmunization. TCDD exposure reduced the production of OVA-specific IgG1 on Days 10 and 14. GC formation in the spleen was also suppressed by TCDD exposure, and the suppression persisted from Day 7 until Day 14. In TCDD-administered mice on Day 7, cellular proliferation in the GCs was significantly suppressed, although apoptosis was not markedly affected. In order to measure high affinity antibody and high-affinity AFCs, the mice were administered TCDD followed by immunization with alum-precipitated (4-hydroxy-3-nitrophenyl) acetyl linked to chicken {gamma}-globulin (NP-CG). The frequency of high-affinity NP-specific AFCs that bind to low-haptenated antigen was clearly shown to be reduced in the spleen on Days 10 and 14. Furthermore, the high-affinity anti-NP IgG1 levels on Days 10 and 14 postimmunization were significantly reduced by TCDD exposure. Taken together, the results of the present study demonstrate that TCDD exposure inhibits the generation of high-affinity AFCs and high-affinity antibody production during the primary humoral immune response, and suggested that these alterations were caused by suppression of antigen-responding B cell proliferation induced by TCDD during GC formation.

Key Words: TCDD, germinal center, high-affinity antibody-forming cell, high-affinity antibody, immune suppression, humoral immunity .


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 LupusHome page
J Li and R. McMurray
Effects of chronic exposure to DDT and TCDD on disease activity in murine systemic lupus erythematosus
Lupus, October 1, 2009; 18(11): 941 - 949.
[Abstract] [PDF]

Home page
 Int ImmunolHome page
K. Nohara, T. Suzuki, K. Ao, H. Murai, Y. Miyamoto, K. Inouye, X. Pan, H. Motohashi, Y. Fujii-Kuriyama, M. Yamamoto, et al.
Constitutively active aryl hydrocarbon receptor expressed in T cells increases immunization-induced IFN-{gamma} production in mice but does not suppress Th2-cytokine production or antibody production
Int. Immunol., July 1, 2009; 21(7): 769 - 777.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
D. A. Weinstein, R. M. Gogal Jr, A. Mustafa, M. R. Prater, and S. D. Holladay
Mid-gestation Exposure of C57BL/6 Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Causes Postnatal Morphologic Changes in the Spleen and Liver
Toxicol Pathol, July 1, 2008; 36(5): 705 - 713.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Nohara, X. Pan, S.-i. Tsukumo, A. Hida, T. Ito, H. Nagai, K. Inouye, H. Motohashi, M. Yamamoto, Y. Fujii-Kuriyama, et al.
Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes
J. Immunol., March 1, 2005; 174(5): 2770 - 2777.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.