Lymphopenia is induced by IFN-α/β stimulation of immune cells but not by triggering of stroma or endothelium. (A) BM chimeras were generated by reconstitution of congenic CD45.1⁺ C57BL/6 mice with CD45.2⁺ IFNAR^–/– BM cells (IFNAR^–/– > WT). Similarly, WT > IFNAR^–/–, IFNAR^–/– > IFNAR^–/–, and WT > WT were obtained. Blood B- and T-cell numbers were counted before and after treatment with poly(I:C). Data are expressed as mean ± SD (n = 3) and are representative of 2 similar experiments. (B) IFN-α/β stimulation has a direct effect on B cells. B cells from WT and IFNAR^–/– mice were labeled with TAMRA or CFSE (left panels) or vice versa (right panels) and were reinjected into WT or IFNAR^–/– recipients. Labeled cells in blood were counted before and after treatment with poly(I:C) and are depicted as a percentage of total B cells (absolute numbers in parentheses). Data are representative of 1 of 3 similar experiments.