Aluminum promotes B1 cells to produce IL-10 and impairs adaptive immune system

Aluminum (Al) is a metal existing in the human body, yet the immunotoxicity of Al remains elusive. To investigate the immunotoxicity of Al, C57BL/6 mice were treated with 200 or 800 ppm Al via drinking water for 3 months, and thereafter the adaptive immune system was evaluated. In addition, mouse splenocytes and human peripheral blood mononuclear cells (PBMC) were treated with Al in vitro to assess the impact of Al in vitro. Treatment with Al reduced the production of IgM and IgG in the serum, and the activation of B cells, CD4 T cells and CD8 T cells in the spleen of mice; treatment with Al in vitro suppressed the production of IgM and IgG, and the activation of B cells, CD4 T cells and CD8 T cells in mouse splenocytes and human PBMC. In vitro co-culture assays suggested that the suppressed adaptive immunity was due to B cells modified by Al. In terms of mechanism, a direct action of Al on B1 cells induced the B1 cells to be IL-10-producing cells and thereby suppressed the adaptive immune system, which was critically dependent on the Jak1/3-STAT signaling. This study reveals that Al suppresses the adaptive immunity via induction of IL-10-producing B1 cells.