Blockage of Wnt/β-catenin signaling by quercetin reduces survival and proliferation of B-1 cells in vitro.

The Wnt/β-catenin signaling pathway has been shown to play an important role in controlling the proliferation, survival and differentiation of hematopoietic cells. Several Wnt/β-catenin signaling components influence hematopoietic cells fate. B-1 cells are self-renewing and spontaneously express both myeloid and lymphoid restricted transcription factors. B-1 lymphocytes play a major role in autoimmunity and are related to CD5(+) B-cell lymphomas and leukemias, such as CLL (chronic lymphocytic leukemia). Herein, we demonstrate that Wnt/β-catenin pathway is important to B-1 cell survival in vitro. The loss of Wnt signals by quercetin treatment induces a reduction in the proliferation and survival of B-1 cells. Furthermore, the quercetin treatment diminishes IL-6 production by peritoneal cells, a cytokine important to the maintenance of B-1 cells in vitro. Importantly, the IL-6 addition to B-1 cell culture prevents cells from apoptosis, even in the presence of quercetin. These data suggest that a deregulation in β-catenin signals could result in alterations in B-1 cell proliferation and differentiation. The correlation between Wnt/β-catenin and IL-6 could point out a mechanism for the expansion of B-1 cells in autoimmune disease and neoplasia.