L. Majlessi et G. Bordenave, Non-overlapping Fas- and BCL-2-regulated death pathways in IgG2a(b)-producing B cells, INT IMMUNOL, 12(7), 2000, pp. 969-976
Using perforin (Pfp)- and/or Fas-dependent cytotoxic pathways, T splenocyte
s from Igh(a/a) mice are able in vivo to totally and chronically eliminate
congenic Igh(b/b) B cells committed to IgG2a(b) production. This phenomenon
leads to a characteristic absence of serum IgG2ab expression (IgG2a(b) all
otype suppression) in, for instance, histocompatible Igh(a/b) or Igh(b/b) m
ice, having neonatally received such T cells. Because the study of the prot
ective role of BCL-2 oncoprotein against Fas-mediated cell death has genera
ted contradictory findings, we examined the possible impact of constitutive
overexpression of transgenic human BCL-2 protein in Igh(b/b) B cells when
the latter were exposed in vivo exclusively with the Fas-dependent, anti-Ig
G2a(b) T cell activity of Igh(a/a) Pfp(0/0) mice. We observed that, despite
high intracellular expression of functional transgenic BCL-2 and no up-reg
ulation of the principal BCL-2 inhibitors in whole Igh(b/b) B cells, total,
chronic and specific IgG2a(b) suppression was exerted by Igha/a Pfp(0/0) c
ytotoxic T cells. These data show that, in this model of negative regulatio
n of Ig production, Fas- and BCL-2-regulated mechanisms belong to non-overl
apping death pathways at the level of IgG2a(b)-producing B cells, targets o
f Igh(a/a) T cell-mediated cytotoxicity, Thus, in these mature B cells, the
Fas signaling-directly operating via caspase 8-does not involve a mitochon
dria-dependent pathway regulated by BCL-2.