Regulation of humoral immunity by FoxP3+ regulatory T cells.

FoxP3(+) T cells play critical roles in the regulation of B-cell function and humoral immune response. FoxP3(+) T cells migrate to the T and B zones of lymphoid organs and the border area between the two areas. Not only can FoxP3(+) T cells suppress B cells directly, but they also suppress B-cell response indirectly through suppressing T-helper cells. Suppression of T-helper or B cells by FoxP3(+) T cells results in limited activation and proliferation of B cells. Consequentially, class-switch recombination and antibody production in B cells are suppressed by FoxP3(+) T cells. Furthermore, FoxP3(+) T cells can kill activated B cells directly. FoxP3(+) T cells can suppress both autoreactive B cells and antibody responses to foreign antigens. The suppressive activity of FoxP3(+) T cells is regulated by cytokines, costimulators and products of pathogens and normal microflora (i.e., Toll-like receptor ligands), which may allow selective regulation of immune responses to self-antigens and commensals versus pathogens by FoxP3(+) cells. Insufficient function or numbers of FoxP3(+) T cells in the body could lead to aberrant B-cell response and autoimmune diseases in multiple organs. Therefore, FoxP3(+) T cells are an important immune component that reins in potentially over-active or self-reactive humoral immunity.