Trypanosoma cruzi Infection Selectively Renders Parasite-Specific IgG super(+) B Lymphocytes Susceptible to Fas/Fas Ligand-Mediated Fratricide

• Published in: The Journal of immunology (1950) 2002-04, Vol.168 (8), p.3965-3973
• Main Authors: Zuniga, E, Motran, C C, Montes, CL, Yagita, H, Gruppi, A
• Format: Article
• Language: English
• Subjects: Fas antigen; FasL protein; Trypanosoma cruzi
• ISSN: 0022-1767

The control of B cell expansion has been thought to be solely regulated by T lymphocytes. We show in this study that Trypanosoma cruzi infection induces up-regulation of both Fas and Fas ligand (FasL) molecules on B cells and renders them susceptible to B cell-B cell killing (referred to as fratricide throughout this paper) mediated via Fas/FasL. Moreover, by in vivo administration of anti-FasL blocking mAb we demonstrate that Fas-mediated B cell apoptosis is an ongoing process during this parasitic infection. We also provide evidence that B cells that have switched to IgG isotype are the preferential targets of B cell fratricide. More strikingly, this death pathway selectively affects IgG super(+) B cells reactive to parasite but not self Ags. Parasite-specific but not self-reactive B cells triggered during this response are rescued after either in vitro or in vivo FasL blockade. Fratricide among parasite-specific IgG super(+) B lymphocytes could impair the immune control of T. cruzi and possibly other chronic protozoan parasites. Our results raise the possibility that the blockade of Fas/FasL interaction in the B cell compartment of T. cruzi-infected mice may provide a means for enhancing antiparasitic humoral immune response without affecting host tolerance.