ToxSci Advance Access originally published online on May 28, 2003
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Toxicological Sciences 74, 315-324 (2003)
Copyright © 2003 by the 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
,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;
CREST, Japan Science and Technology, Kawaguchi 332-0012, Japan; and
Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-0044, Japan
In the humoral immune response to an 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 this paper we investigate 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. Then the GC formation in the spleen and OVA-specific antibodies in the plasma, was 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 
-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 this paper demonstrate that TCDD exposure inhibits the generation of high-affinity AFCs and high-affinity antibody production during the primary humoral immune response and suggest that these alterations were caused by the 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.
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