Here, we report that the number of CD11c⁺CD3⁻ B220⁻ cells increases in autoimmune-prone male (NZW × BXSB)F1 (W/BF1) mice with age. The CD11c⁺CD3⁻B220⁻ cells from W/BF1 mice show a typical stellate shape and induce the proliferation of T cells. In the CD11c⁺CD3⁻B220⁻ cells from W/BF1 mice, CD11b (Mac-1α), NK 1.1, and CD95 (Fas) are upregulated in comparison with normal mice, while the expression of CD8α, CD117 (c-kit), CD135 (Flk-2/Flt-3), and Sca-1 decreases. There is a significant increase in Flt-3L (FL) mRNA in the bone marrow of W/BF1 mice with age. Moreover, activated hemopoietic cells express high levels of FL. The injection of CD11c⁺CD3⁻B220⁻ cells from old W/BF1 mice to young W/BF1 mice transiently induces autoimmune disease (thrombocytopenia). These results suggest that hyperproduction of FL from activated hemopoietic cells induces a dramatic increase in the number of dendritic cells in aged W/BF1 mice, followed by the acceleration of autoimmunity.