The Journal of Experimental Medicine
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J. Exp. Med., Volume 186, Number 12, December 15, 1997 1997-2004

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

By Mitsuru Matsumoto,*Dagger Yang-Xin Fu,*§ Hector Molina,*Dagger Guangming Huang,*par Jinho Kim,*§ Dori A. Thomas,*Dagger Moon H. Nahm,*§ and David D. Chaplin*Dagger par

From the * Center for Immunology and the Department of Dagger  Internal Medicine, the § Department of Laboratory Medicine/Pathology, and the par  Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110

In mice deficient in either lymphotoxin alpha  (LT-alpha ) 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-alpha and TNFR-I in the establishment of spleen FDC and GC structure by using reciprocal bone marrow (BM) transfer. When LT-alpha -deficient mice were reconstituted with wild-type BM, FDC organization and the ability to form GC were restored, indicating that the LT-alpha -expressing cells required to establish organized FDC are derived from BM. The role of LT-alpha in establishing organized FDC structure was further investigated by the transfer of complement receptor 1 and 2 (CR1/2)-deficient BM cells into LT-alpha -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-alpha -deficient recipient. Thus, expression of LT-alpha in the BM-derived cells, but not in the non-BM-derived cells, is required for the maturation of FDC from non-BM precursor cells. In contrast, when TNFR-I-deficient mice were reconstituted with wild-type 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-alpha -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-alpha -expressing BM-derived cells and by TNFR-I-expressing non-BM-derived cells.


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