Direct suppression of antibody responses by chlorinated dibenzodioxins in cultured spleen cells from (C57BL/6 × C3H)F1 and DBA/2 mice

2,3,7,8-Tetrachlorodibenzo-p-dioxin-Mediated Impairment of B Cell Differentiation Involves Dysregulation of Paired Box 5 (Pax5) Isoform, Pax5a

“…Previous studies have demonstrated that B cells are directly targeted by TCDD (Holsapple et al, 1986;Sulentic et al, 1998) and that the AHR is required for suppression of the IgM response (Vecchi et al, 1983;Kerkvliet et al, 1990;Sulentic et al, 1998). However, the molecular mechanism responsible for the suppression of humoral immune responses by TCDD remains undeciphered.…”

“…As a result, suppression of Pax5 promotes the terminal B cell differentiation program (Nera et al, 2006). The impairment of the functional outcome of B cell differentiation (i.e., IgM secretion) by TCDD was previously shown to occur at TCDD concentrations that only modestly suppressed B cell proliferation, giving rise to the notion that TCDD impairs terminal B cell differentiation (Holsapple et al, 1986;Luster et al, 1988). However, little is known about the mechanism by which TCDD-mediated suppression of B cell differentiation occurs and what other aspects of B cell differentiation, besides the IgM response, are affected by TCDD treatment.…”

“…This suppression is characterized by a striking reduction in plasma cell formation and IgM secretion, and it is mediated through a direct effect by TCDD on B cells (Holsapple et al, 1986;Sulentic et al, 1998). TCDD serves as a ligand for the basic-helix-loop-helix/periodicity/ aryl hydrocarbon receptor (AHR) nuclear translocator (ARNT)/simple-minded family protein, AHR (Hankinson, 1995).…”

Immunological Effects of Chlorinated Dibenzo-p-Dioxins

“…Furthermore, when in vitro effects ofTCDD are observed, they may be inconsistent with the in vivo immunotoxic effects of TCDD. For example, in vitro suppression of the antibody response to SRBC has been reported by some laboratories to be independent of the AhR (39,40), whereas suppression of this response in vivo is clearly AhR-dependent. Although the basis for the discrepancies between in vivo and in vitro effects is not known, differences in culture conditions may be partially responsible since the in vitro effects of TCDD on lymphoid cells appear to be influenced by unknown factors present in serum-supplemented tissue culture media (41,42).…”

“…While T-cell responses appear to be resistant to direct effects of TCDD, several laboratories have reported that TCDD directly alters B-lymphocyte functions in vitro (13,40,43,44). Studies using both murine and human B cells suggest that TCDD alters the terminal differentiation of B cells into antibody-secreting plasma cells without altering B-cell proliferation (43)(44)(45).…”