title: 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.
abstract: 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.
authors.affiliation: Center for Immunology and the Department of, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Y X
authors.initials: YX
authors.lastname: Fu
authors.forename: H
authors.initials: H
authors.lastname: Molina
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: D A
authors.initials: DA
authors.lastname: Thomas
authors.forename: M H
authors.initials: MH
authors.lastname: Nahm
authors.forename: D D
authors.initials: DD
authors.lastname: Chaplin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D003713:Dendritic Cells / Q000166:cytology*; D018858:Germinal Center / Q000166:cytology; D007124:Immunoenzyme Techniques; D008233:Lymphotoxin-alpha / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D013154:Spleen / Q000166:cytology
chemical_list: D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor