Abstract
The role of B-cell-activating factor (BAFF) in B-lymphocyte biology has been comprehensively studied, but its contributions to innate immunity remain unclear. Natural killer (NK) cells form the first line of defense against viruses and tumors, and have been shown to be defective in patients with systemic lupus erythematosus (SLE). The link between BAFF and NK cells in the development and progression of SLE remains unstudied. By assessing NK cell numbers in wild-type (WT), BAFF-/- (BAFF deficient), BAFF-R-/- (BAFF receptor deficient), TACI-/- (transmembrane activator and calcium modulator and cyclophilin ligand interactor deficient), BCMA-/- (B-cell maturation antigen deficient) and BAFF transgenic (Tg) mice, we observed that BAFF signaling through BAFF-R was essential for sustaining NK cell numbers in the spleen. However, according to the cell surface expression of CD27 and CD11b on NK cells, we found that BAFF was dispensable for NK cell maturation. Ex vivo and in vivo models showed that NK cells from BAFF-/- and BAFF Tg mice produced interferon-γ and killed tumor cells at a level similar to that in WT mice. Finally, we established that NK cells do not express receptors that interact with BAFF in the steady state or in the BAFF Tg mouse model of SLE. Our findings demonstrate that BAFF has an indirect effect on NK cell homeostasis and no effect on NK cell function.