hsBAFF enhances activity of NK cells by regulation of CD4(+) T lymphocyte function

B cell activating factor belonging to the TNF family (BAFF, also called BLyS, TALL-1, THANK, or zTNF4) is an important survival factor for B cells, and is able to regulate T cell activation. Recently, we have demonstrated that human soluble BAFF (hsBAFF) potently elevates NK cell activity of murine splenic cells in vivo. In this study, we further show that hsBAFF markedly enhanced NK cell activity of in vitro mouse splenic cells. Purified NK cell activities treated with hsBAFF in the presence of IL-2 or IFN-gamma, but not with hsBAFF alone were obviously elevated. hsBAFF strongly increased the activity of NK cells co-incubated with mixed T and B lymphocytes or T lymphocytes alone, but not with B lymphocytes alone. We also found that culture supernatants, from mixed T and B lymphocytes or T lymphocytes alone, but not from B lymphocytes alone post-hsBAFF treatment, effectively increased NK cell activity, and noticed that IL-2 and IFN-gamma levels significantly increased in the culture supernatants of hsBAFF-treated T lymphocytes. Of importance, we pinpointed that hsBAFF elicited robust population of CD4(+) T lymphocytes in vitro, and further demonstrated that hsBAFF induced significantly high IL-2 and IFN-gamma secretion of CD4(+) T lymphocytes. These findings indicate that hsBAFF results in the elevation of NK cell activity by regulation of CD4(+) T lymphocytes contributing to IL-2 and IFN-gamma generation.