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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.

Matsumoto M, Fu YX, Molina H, Huang G, Kim J, Thomas DA, Nahm MH, Chaplin DD - J. Exp. Med. (1997)

Bottom Line: 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.This indicates that TNFR-I expression on non-BM-derived cellular components is necessary for the establishment of these lymphoid structures.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Immunology and the Department of, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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.

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FDC clusters induced after BM transfers are non–BM-derived. When BM from CR1/2-deficient mice was used to reconstitute LT-α–deficient mice, FDC clusters, which stained with anti-CR1 mAb, formed. These FDC clusters supported the development of PNA+ GC. After BM transfer,  mice were immunized and spleens were harvested as described in Fig. 1. (A) Staining was with anti-CR1 (blue) and anti-B220 (brown). (B) Staining was  with PNA (blue) and anti-B220 (brown). Original magnification, ×100.
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Figure 2: FDC clusters induced after BM transfers are non–BM-derived. When BM from CR1/2-deficient mice was used to reconstitute LT-α–deficient mice, FDC clusters, which stained with anti-CR1 mAb, formed. These FDC clusters supported the development of PNA+ GC. After BM transfer, mice were immunized and spleens were harvested as described in Fig. 1. (A) Staining was with anti-CR1 (blue) and anti-B220 (brown). (B) Staining was with PNA (blue) and anti-B220 (brown). Original magnification, ×100.

Mentions: To further demonstrate the role of LT-α as a signal required to establish organized FDC structure and to investigate the cell lineage of FDC, we used BM cells from CR1/ 2-deficient mice to reconstitute irradiated LT-α–deficient mice. In this context, donor CR1/2-deficient BM-derived cells are LT-α wild type, but can be distinguished from the LT-α–deficient recipient cells by their failure to stain with anti-CR1 mAb (36). After reconstitution, spleen sections were stained with anti-CR1 mAb and PNA to assay for the presence of FDC clusters and GC. Similar to the results obtained after transfer of wild-type BM cells, clustered FDC were identified with anti-CR1 mAb after transfer of CR1/ 2-deficient BM (Fig. 2 A). These FDC were able to support the formation of typical CR1/2-expressing GC (Fig. 2 B). These results clearly indicate that the clustered FDC induced in these BM-chimeric mice are derived from the LT-α–deficient recipient, and that LT-α provides a signal that supports the development of FDC clusters. These results also indicate that the lack of organized FDC structure in LT-α–deficient mice is a plastic characteristic determined by the LT-α expression status of the BM-derived cells populating the animal.


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.

Matsumoto M, Fu YX, Molina H, Huang G, Kim J, Thomas DA, Nahm MH, Chaplin DD - J. Exp. Med. (1997)

FDC clusters induced after BM transfers are non–BM-derived. When BM from CR1/2-deficient mice was used to reconstitute LT-α–deficient mice, FDC clusters, which stained with anti-CR1 mAb, formed. These FDC clusters supported the development of PNA+ GC. After BM transfer,  mice were immunized and spleens were harvested as described in Fig. 1. (A) Staining was with anti-CR1 (blue) and anti-B220 (brown). (B) Staining was  with PNA (blue) and anti-B220 (brown). Original magnification, ×100.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199170&req=5

Figure 2: FDC clusters induced after BM transfers are non–BM-derived. When BM from CR1/2-deficient mice was used to reconstitute LT-α–deficient mice, FDC clusters, which stained with anti-CR1 mAb, formed. These FDC clusters supported the development of PNA+ GC. After BM transfer, mice were immunized and spleens were harvested as described in Fig. 1. (A) Staining was with anti-CR1 (blue) and anti-B220 (brown). (B) Staining was with PNA (blue) and anti-B220 (brown). Original magnification, ×100.
Mentions: To further demonstrate the role of LT-α as a signal required to establish organized FDC structure and to investigate the cell lineage of FDC, we used BM cells from CR1/ 2-deficient mice to reconstitute irradiated LT-α–deficient mice. In this context, donor CR1/2-deficient BM-derived cells are LT-α wild type, but can be distinguished from the LT-α–deficient recipient cells by their failure to stain with anti-CR1 mAb (36). After reconstitution, spleen sections were stained with anti-CR1 mAb and PNA to assay for the presence of FDC clusters and GC. Similar to the results obtained after transfer of wild-type BM cells, clustered FDC were identified with anti-CR1 mAb after transfer of CR1/ 2-deficient BM (Fig. 2 A). These FDC were able to support the formation of typical CR1/2-expressing GC (Fig. 2 B). These results clearly indicate that the clustered FDC induced in these BM-chimeric mice are derived from the LT-α–deficient recipient, and that LT-α provides a signal that supports the development of FDC clusters. These results also indicate that the lack of organized FDC structure in LT-α–deficient mice is a plastic characteristic determined by the LT-α expression status of the BM-derived cells populating the animal.

Bottom Line: 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.This indicates that TNFR-I expression on non-BM-derived cellular components is necessary for the establishment of these lymphoid structures.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Immunology and the Department of, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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.

Show MeSH
Related in: MedlinePlus