DISTINCT ROLES OF LYMPHOTOXIN-ALPHA AND THE TYPE-I TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR IN THE ESTABLISHMENT OF FOLLICULAR DENDRITIC CELLS FROM NON-BONE MARROW-DERIVED CELLS

In mice deficient in either lymphotoxin alpha (LT-alpha) or type I tum or necrosis factor receptor (TNFR-I), organized clusters of follicular dendritic cells (FDC) and germinal centers (GC) are absent from the s pleen. We investigated the role of LT-alpha and TNFR-I in the establis hment of spleen FDC and GC structure by using reciprocal bone marrow ( BM) transfer, When LT-alpha-deficient mice were reconstituted with wil d-type BM, FDC organization and the ability to form GC were restored, indicating that the LT-alpha-expressing cells required to establish or ganized FDC are derived from BM. The role of LT-alpha in establishing organized FDC structure was further investigated by the transfer of co mplement receptor 1 and 2 (CR1/2)-deficient BM cells into LT-alpha-def icient mice. Organized FDC were identified with both the FDC-M1 and an ti-CR1 monoclonal antibodies in these BM-chimeric mice, indicating tha t these cells were derived from the LT-alpha-deficient recipient. Thus , expression of LT-alpha in the BM-derived cells, but not in the non-B M-derived cells, is required for the maturation of FDC from non-BM pre cursor cells. In contrast, when TNFR-I-deficient mice were reconstitut ed with wild-type BM, they showed no detectable FDC clusters or GC for mation, This indicates that TNFR-I expression on non-BM-derived cellul ar components is necessary for the establishment of these lymphoid str uctures. TNFR-I-deficient BM was able to restore FDC organization and GC formation in LT-alpha-deficient mice, indicating that formation of these structures does not require TNFR-I expression on BM-derived cell s. The data in this study demonstrate that FDC organization and GC for mation are controlled by both LT-alpha-expressing BM-derived cells and by TNFR-I-expressing non-BM-derived cells.