2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated disruption of the CD40 ligand-induced activation of primary human B cells

Journal Article · Thu Sep 15 04:00:00 EDT 2011 · Toxicology and Applied Pharmacology

OSTI ID:21587839

Suppression of the primary antibody response is particularly sensitive to suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice; however, surprisingly little is known concerning the effects of TCDD on humoral immunity or B cell function in humans. Results from a limited number of previous studies, primarily employing in vitro activation models, suggested that human B cell effector function is suppressed by TCDD. The present study sought to extend these findings by investigating, in primary human B cells, the effects of TCDD on several critical stages leading to antibody secretion including activation and plasmacytic differentiation using an in vitro CD40 ligand activation model. These studies revealed important differences in the response of human and mouse B cells to TCDD, the most striking being altered expression of plasmacytic differentiation regulators, B lymphocyte-induced maturation protein 1 and paired box protein 5, in mouse but not human B cells. The activation of human B cells was profoundly impaired by TCDD, as evidenced by decreased expression of activation markers CD80, CD86, and CD69. The impaired activation correlated with decreased cell viability, which prevented the progression of human B cells toward plasmacytic differentiation. TCDD treatment also attenuated the early activation of mitogen-activated protein kinases (MAPK) and Akt signaling in human B cells. Collectively, the present study provided experimental evidence for novel mechanisms by which TCDD impairs the effector function of primary human B cells. - Highlights: > In this study primary human and mouse B cell toxicity to TCDD was compared. > TCDD altered the expression of Blimp-1 and Pax5 in mouse but not human B cells. > TCDD markedly suppressed human B cell activation as characterized by CD80, CD86 and CD69 expression. > TCDD inhibited ERK, p38, and Akt phosphorylation in human B cells.

• OSTI ID: 21587839
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 255; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DIOXIN
HETEROCYCLIC COMPOUNDS
HUMAN POPULATIONS
IN VITRO
INHIBITION
LEUKOCYTES
LIGANDS
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
POPULATIONS
RODENTS
SOMATIC CELLS
TOXICITY
VERTEBRATES