CONICET | Buscador de Institutos y Recursos Humanos

Protective immune responses require specific and balanced responses to clear pathogens and tumors and yet maintaining tolerance to self-antigens. Induction and maintenance of T cell tolerance is achieved by pathways triggered by different pairs of receptors and ligands. Among them, PD-1 (programmed death-1) and its ligands PD-L1 and PD-L2 can limit effector T cell responses preventing immune-mediated tissue damage. The general aim of our work is to evaluate the PD-1-PD-L1 pathway on B cell immunity. We first analyzed the expression of PD-1, PD-L1 and PD-L2 on different B cell subsets. All follicular (FO) and marginal zone (MZ) B cells expressed similar levels of PD-1 (MFI 8,4±0,3 and 9,6±0,5 respectively) and few MZ and FO B cells expressed PD-L2 (1,3% and 3,9% respectively p=0,0036). Interestingly, all MZ B cells expressed PD-L1 and its expression was significant higher than on FO B cells (p=0,0019). By immunofluorescence, we observed a B220hiPD-L1hi population in the marginal zone of spleen sections of C57BL6 mice. Stimuli like LPS, CpG and tripomastigotes of Trypanosoma cruzi considerably increased the expression of PD-L1 on B cells. The high expression of PD-L1 by MZ B cells correlates with high production of IL-6 and IL-10 since MZ B cells produce higher concentrations of IL-6 and IL-10 in basal condition and after LPS stimulation, in comparison to FO B cells. PD-L1 and PD-L2 can signal bi-directionally by engaging PD-1 on T cells which can deliver signals into PD-L1/2-expressing cells. Thus, MZ B cells could regulate immunity or be regulated via PD-1/PD-L1 pathway, particularly upon activation during an infectious process. Functional studies are currently being performed in our laboratory.