International Immunology, Vol. 12, No. 7, 969-976,
July 2000
© 2000 Japanese Society for Immunology
Non-overlapping Fas- and BCL-2-regulated death pathways in IgG2ab-producing B cells
Unité d'Immunophysiologie Moléculaire, Institut Pasteur, 25 rue du Docteur-Roux, 75724 Paris Cedex 15, France
Correspondence to: G. Bordenave
Using perforin (Pfp)- and/or Fas-dependent cytotoxic pathways, T splenocytes from Igha/a mice are able in vivo to totally and chronically eliminate congenic Ighb/b B cells committed to IgG2ab production. This phenomenon leads to a characteristic absence of serum IgG2ab expression (IgG2ab allotype suppression) in, for instance, histocompatible Igha/b or Ighb/b mice, having neonatally received such T cells. Because the study of the protective role of BCL-2 oncoprotein against Fas-mediated cell death has generated contradictory findings, we examined the possible impact of constitutive overexpression of transgenic human BCL-2 protein in Ighb/b B cells when the latter were exposed in vivo exclusively with the Fas-dependent, anti-IgG2ab T cell activity of Igha/a Pfp0/0 mice. We observed that, despite high intracellular expression of functional transgenic BCL-2 and no up-regulation of the principal BCL-2 inhibitors in whole Ighb/b B cells, total, chronic and specific IgG2ab suppression was exerted by Igha/a Pfp0/0 cytotoxic T cells. These data show that, in this model of negative regulation of Ig production, Fas- and BCL-2-regulated mechanisms belong to non-overlapping death pathways at the level of IgG2ab-producing B cells, targets of Igha/a T cell-mediated cytotoxicity. Thus, in these mature B cells, the Fas signaling—directly operating via caspase 8—does not involve a mitochondria-dependent pathway regulated by BCL-2.
Keywords: CD95, cytotoxicity, death pathway, Ig allotype, perforin