Follicular dendritic cell (FDC)‐FcγRIIB levels are up‐regulated 1–3 days after challenge of actively immunized mice with Ag. This kinetics suggested that memory cells are not driving this response, prompting the hypothesis that immune complex (IC)‐FDC interactions lead to FDC activation. To test this, mice passively immunized with anti‐OVA Ab were OVA challenged to produce IC. After 3 days, levels of IC, FcγRIIB, ICAM‐1, and VCAM‐1 on FDC were analyzed. FDC were also stimulated with IC in vitro, and mRNA for FcγRIIB, ICAM‐1, and VCAM‐1 was quantified by quantitative RT‐PCR. IC labeling in passively immunized WT and FcγRIIB^–/– mice revealed five to six FDC‐reticula per LN midsagittal section. In WT mice, these IC‐bearing FDC‐reticula corresponded with FDC‐reticula labeling for FcγRIIB, ICAM‐1, and VCAM‐1. Increases in these molecules on IC‐stimulated FDC were confirmed by flow cytometry. In marked contrast, in FcγRIIB^–/– mice, no increased VCAM‐1 or ICAM‐1 was seen on IC‐bearing FDC‐reticula or on purified FDC. Addition of IC in vitro resulted in dramatic increases in mRNA for FcγRIIB, ICAM‐1 and VCAM‐1 in WT FDC, but not in FDC from FcγRIIB^–/– mice, 2.4G2‐pretreated WT FDC, B cells, or macrophages. Thus, although FDC‐FcγRIIB was not essential for IC trapping, engagement of FDC‐FcγRIIB with IC initiated an FDC activation pathway.