Zuñiga Elina, Motran Claudia C, Montes Carolina L, Yagita Hideo, Gruppi Adriana
Department of Clinical Biochemistry, Faculty of Chemical Science, National University of Cordoba, Cordoba, Argentina.
J Immunol. 2002 Apr 15;168(8):3965-73. doi: 10.4049/jimmunol.168.8.3965.
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(+) 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(+) 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.
B细胞扩增的控制一直被认为完全由T淋巴细胞调节。我们在本研究中表明，克氏锥虫感染会诱导B细胞上Fas和Fas配体（FasL）分子的上调，并使它们易于受到通过Fas/FasL介导的B细胞 - B细胞杀伤作用（在本文中简称为自相残杀）。此外，通过体内给予抗FasL阻断单克隆抗体，我们证明Fas介导的B细胞凋亡是这种寄生虫感染过程中的一个持续过程。我们还提供证据表明，已转换为IgG同种型的B细胞是B细胞自相残杀的优先靶标。更引人注目的是，这种死亡途径选择性地影响对寄生虫而非自身抗原具有反应性的IgG(+) B细胞。在体外或体内进行FasL阻断后，在此反应过程中触发的寄生虫特异性而非自身反应性B细胞得以挽救。寄生虫特异性IgG(+) B淋巴细胞之间的自相残杀可能会损害克氏锥虫以及可能其他慢性原生动物寄生虫的免疫控制。我们的结果提出了一种可能性，即阻断克氏锥虫感染小鼠B细胞区室中的Fas/FasL相互作用可能提供一种在不影响宿主耐受性的情况下增强抗寄生虫体液免疫反应的方法。
