The immunomodulatory function of human amniotic fluid stromal cells on B lymphocytes

Abstract

Current treatments for B cell-mediated disease are mainly based on global B cell depletion, thereby eliminating pathogenic B cells as well as Breg subsets. A more refined modulation of B cell activity could prove beneficial for patient treatment.Objective:To investigate the immunomodulatory function of human amniotic fluid stromal cells (hAFSCs) on different subpopulation of B lymphocytes.Methods:hAFSCs were isolated and cultured and identified by characteristic phenotypic markers. After coculture of B lymphocytes with hAFSCs, the activation, proliferation, differentiation, as well as apoptosis, cell cycle, and expression of the inhibitory costimulatory molecules B7H1, B7H3, and B7H4 of B lymphocytes were examined in vitro.Results:Coculture with hAFSCs significantly decreased the expression of CD80/CD86, Ki-67 and CFSE expression, on activated B lymphocytes. These might be due to the inhibition of B lymphocyte apoptosis and cell cycle arrest. In activated B lymphocytes, coculture with hAFSCs resulted in a reduced proportion of memory B and plasma cells, reduced amounts of immunoglobulins. hAFSCs could balance the B1 to B2 cell subpopulation ratio. hAFSCs could inhibit the expression of the negative co-inhibitory molecule B7H4 and PD-L1 on the activated B lymphocytes.Conclusion:hAFSCs could inhibit B cell activation, proliferation, and subpopulation differentiation. These might be due to their affect on B cell apoptosis, cell cycle and the expression of costimulatory molecules of human B lymphocytes. Our experiment provided the evidence for hAFSCs as ideal seed cells with therapeutic potential for treating humoral immunity disorders, which were mainly mediated by B lymphocytes.