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Development of an in vitro system to assess the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on B lymphocyte activation and differentiation

Thesis/Dissertation ·
OSTI ID:7243101
Humoral immunity appears to be a sensitive target for chemical induced immunosuppression. Therefore, in vitro methodologies were developed to assess the effects of environmental chemicals on B lymphocyte activation and differentiation. The environmental chemical, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was used to develop these methodologies. The in vitro humoral immune response of purified B cells to the T-independent antigen TNP-LPS was suppressed in a dose dependent manner with an EC{sub 50} of 10 nM TCDD. A polyclonal activation system using anti-immunoglobulin and T cell derived factors was used to further analyze B lymphocyte suppression by TCDD. The activation and proliferation responses of B lymphocytes were not affected by TCDD as monitored by the incorporation of {sup 3}H-uridine and {sup 3}H-thymidine or expression of the cell surface markers Ia and the IL-2 receptor. Terminal differentiation was selectively inhibited by TCDD as assessed by a dose dependent inhibition of immunoglobulin synthesis and expression of the cell surface marker PC.2. Protein phosphorylation, an early event in lymphocyte activation, was altered by exposure to TCDD and was associated with a dose dependent increase in the activity of tyrosine-specific protein kinases.
Research Organization:
North Carolina Univ., Chapel Hill, NC (USA)
OSTI ID:
7243101
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTIGENS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DIOXIN
DOSE-RESPONSE RELATIONSHIPS
GLOBULINS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
IMMUNE REACTIONS
IMMUNITY
IMMUNOGLOBULINS
IMMUNOSUPPRESSION
IN VITRO
ISOTOPE APPLICATIONS
LEUKOCYTES
LYMPHOCYTES
MATERIALS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PROTEINS
PYRIMIDINES
RIBOSIDES
SOMATIC CELLS
SYNTHESIS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
URACILS
URIDINE