Interleukin-4 biases differentiation of B cells from Trypanosoma cruzi-infected mice and restrains their fratricide: role of Fas ligand down-regulation and MHC class II-transactivator up-regulation.
In the present work, we demonstrate that interleukin (IL)-4 is able to rescue B cells from Trypanosoma cruzi-infected mice, counteracting the strong apoptotic signals that these cells received in vivo. We have observed that IL-4 restrains the apoptosis of immunoglobulin (Ig)M(+) and IgG(+) B cells from infected and normal mice without inducing them to proliferate. In addition, IL-4 does not modify the quantity or quality of the antibodies secreted by B cells from infected mice, as it blocks their terminal differentiation to plasma cells and favors memory pathway. It is interesting that the protective effect of IL-4 over B cells from infected mice is mediated, at least partly, by the down-regulation of Fas ligand (FasL) expression, which leads to interference in the apoptosis executed by these B cells through the Fas/FasL death pathway. Accordingly, a marked up-regulation of the "FasL gene repressor" class II transactivator was observed, suggesting that this would be one mechanism underlying the IL-4-mediated FasL down-regulation.
Acosta Rodriguez
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Inmunología, Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Ciudad Universitaria, Haya de la Torre Medina Allende, Cordoba (5000), Argentina.
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000469:parasitology*; D002454:Cell Differentiation / Q000187:drug effects; D014355:Chagas Disease; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D015847:Interleukin-4 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000096:biosynthesis / Q000187:drug effects; D014349:Trypanosoma cruzi
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C083728:MHC class II transactivator protein; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D015847:Interleukin-4