Follicular dendritic cells (FDCs) form a reticular FDC network in the lymphoid follicle that is essential for the retention and presentation of native antigens in the form of antigen-antibody immune complexes (ICs) to B cells during secondary immune response. Although the presence of migrating precursors of FDCs has been hypothesized, their entity has not been elucidated. Here we report the identification of murine splenic CD19CD11c CD35B220 cells as an inducer of FDC network formation. We demonstrated that CD19-CD11cCD35 B220 cells, together with stromal cells, had the remarkable ability to form lymphoid-follicle-like structures that contained B220FDC-M1 reticular cells originally derived from CD19-CD11cCD35B220 cells in the CD35 reticulum. Our results indicate that CD19CD11c CD35B220 cells function as an inducer of FDC network formation and that the interaction between CD19CD11c CD35B220 cells and stromal cells is required to initiate lymphoid follicle formation. © 2007 by The American Society of Hematology.