We demonstrated that GDH induces proliferation of splenic B cells from normal mice in a T-independent but macrophage(Mf)-dependent fashion. GDH-stimulated Mf produce cytokines such as IL-6, IL-10 and Baff, involved in B cell proliferation and PC differentiation. The aim of this work was to determine if GDH drives B cell differentiation into PC and the molecules involved in this process. For that, normal murine B cells were cultured with medium or 20 mg/ml GDH in presence of Mf. By FACS, we determined that GDH stimulation increases the percentage and absolute number of Syndecan-1+ cells (PC). Accordingly, GDH increases in B cells the levels of mRNA of BLIMP-1 and XBP-1, transcription factors involved in PC differentiation. Additionally, we determined higher levels of IgG (1300pg/ml) and IgM (1400pg/ml) in the supernatants of GDH-stimulated cultures in comparison to controls (IgG:750pg/ml, IgM:450pg/ml). By blocking assays, we determined that GDH-induced B cell proliferation was dependent on Il-6, IL-10 and Baff, and that BAFF was not implicated in PC differentiation. Our results indicate that this parasite protein probably contributes to the unspecific hypergammaglobulinemia observed during T. cruzi infection by enhancing B cell proliferation and Ab-secreting cells development.
