In mice deficient in either lymphotoxin α (LT-α) or type I tumor necrosis factor receptor (TNFR-I), organized clusters of follicular dendritic cells (FDC) and germinal centers (GC) are absent from the spleen. We investigated the role of LT-α and TNFR-I in the establishment of spleen FDC and GC structure by using reciprocal bone marrow (BM) transfer. When LTα- deficient mice were reconstituted with wild-type BM, FDC organization and the ability to form GC were restored, indicating that the LT-α-expressing cells required to establish organized FDC are derived from BM. The role of LT-α in establishing organized FDC structure was further investigated by the transfer of complement receptor 1 and 2 (CR1/2)-deficient BM cells into LT-α- deficient mice. Organized FDC were identified with both the FDC-M1 and anti- CR1 monoclonal antibodies in these BM-chimeric mice, indicating that these cells were derived from the LT-α-deficient recipient. Thus, expression of LT-α in the BM-derived cells, but not in the non-BM-derived cells, is required for the maturation of FDC from nonBM precursor cells. In contrast, when TNFR-I-deficient mice were reconstituted with wildtype BM, they showed no detectable FDC clusters or GC formation. This indicates that TNFR-I expression on non-BM-derived cellular components is necessary for the establishment of these lymphoid structures. TNFR-I-deficient BM was able to restore FDC organization and GC formation in LT-α-deficient mice, indicating that formation of these structures does not require TNFR-I expression on BM- derived cells. The data in this study demonstrate that FDC organization and GC formation are controlled by both LT-α-expressing BM-derived cells and by TNFR-I-expressing non-BM-derived cells.