Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts B-cell lymphopoiesis and exacerbates autoimmune disease in 24-week-old SNF1 mice.
Female SNF(1) hybrid mice spontaneously develop an immune complex-mediated glomerulonephritis as early as 24 weeks of age, whereas the disease onset in males is much slower. Further, a rise in concentration of glomerulus-specific autoantibodies via autoreactive B cells is critical to progression of the disease in this strain. Environmental factors contributing to the onset or degree of such autoimmunity are of interest yet poorly understood. In the present study, time-pregnant SWR x NZB dams (10/treatment) were gavaged on gestational 12 with 40 or 80 mg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the SNF(1) offspring were evaluated at 24 weeks of age. Bone marrow B220(low)CD24(-)AA4.1(+) committed B lineage progenitors were increased in female offspring by TCDD, however, committed progenitors and pro-B cells were decreased in males. Splenic marginal zone B cells (CD21(hi)CD24(low-int)) were decreased and follicular B cells (CD21(int)CD24(low)) were increased across sex by prenatal TCDD, whereas transitional-2 B cells (CD21(int)CD24(hi)) and (CD23(low-int) CD1(low-int)) were decreased in males only. Antibodies to double-stranded DNA were significantly increased across sex by TCDD. Anti-IgG and anti-C3 immune complex renal deposition was visibly worsened in females, and present in TCDD-treated males. These data suggest that developmental exposure to TCDD permanently and differentially alters humoral immune function by sex, and exacerbates a type III hypersensitivity lupus-like autoimmune disease in genetically predisposed mice.
Mustafa
Amjad
A
Center for Molecular Medicine and Infectious, Diseases, Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24060-0442, USA.
Holladay
Steven D
SD
Witonsky
Sharon
S
Zimmerman
Kurt
K
Reilly
Christopher M
CM
Sponenberg
D Phillip
DP
Weinstein
Danielle A
DA
Karpuzoglu
Ebru
E
Gogal
Robert M
RM
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D000072317:Polychlorinated Dibenzodioxins