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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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Failure to restore organized FDC clusters and development of GC in TNFR-I–deficient mice by transplantation with normal BM. (A and C)  TNFR-I–deficient mice reconstituted with wild-type BM showed no detectable FDC clusters or GC. (B and D) Wild-type mice reconstituted with  TNFR-I–deficient BM showed FDC clusters and GC formation. After BM transfer, mice were immunized and spleens were harvested as described in  Fig. 1. (A and B) Staining was with anti-CR1 antibody 8C12 (blue) and anti-B220 (brown). (C and D) Staining was with PNA (blue) and anti-B220  (brown). Original magnification, ×100.
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Figure 3: Failure to restore organized FDC clusters and development of GC in TNFR-I–deficient mice by transplantation with normal BM. (A and C) TNFR-I–deficient mice reconstituted with wild-type BM showed no detectable FDC clusters or GC. (B and D) Wild-type mice reconstituted with TNFR-I–deficient BM showed FDC clusters and GC formation. After BM transfer, mice were immunized and spleens were harvested as described in Fig. 1. (A and B) Staining was with anti-CR1 antibody 8C12 (blue) and anti-B220 (brown). (C and D) Staining was with PNA (blue) and anti-B220 (brown). Original magnification, ×100.

Mentions: TNFR-I–deficient mice also lack FDC clusters and spleen GC formation (25, 26). To investigate the mechanism of this structural defect in the TNFR-I–deficient mice, we performed similar reciprocal BM transfer experiments. In contrast to the LT-α–deficient mice, reconstitution of TNFR-I–deficient mice with wild-type BM did not restore the organization of FDC clusters or the formation of GC (Fig. 3, A and C). This suggests that development of normal clusters of FDC in the spleen requires TNFR-I expression on some radioresistant non–BM-derived component(s) in the recipient mouse, most likely a cellular element within the spleen itself. Alternatively, the failure to restore FDC clusters in TNFR-I–deficient mice after transfer of normal BM might indicate that essential TNFR-I–dependent interactions may be required within a developmental window before 8–12 wk of age, when these BM transfers were performed.


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)

Failure to restore organized FDC clusters and development of GC in TNFR-I–deficient mice by transplantation with normal BM. (A and C)  TNFR-I–deficient mice reconstituted with wild-type BM showed no detectable FDC clusters or GC. (B and D) Wild-type mice reconstituted with  TNFR-I–deficient BM showed FDC clusters and GC formation. After BM transfer, mice were immunized and spleens were harvested as described in  Fig. 1. (A and B) Staining was with anti-CR1 antibody 8C12 (blue) and anti-B220 (brown). (C and D) 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 3: Failure to restore organized FDC clusters and development of GC in TNFR-I–deficient mice by transplantation with normal BM. (A and C) TNFR-I–deficient mice reconstituted with wild-type BM showed no detectable FDC clusters or GC. (B and D) Wild-type mice reconstituted with TNFR-I–deficient BM showed FDC clusters and GC formation. After BM transfer, mice were immunized and spleens were harvested as described in Fig. 1. (A and B) Staining was with anti-CR1 antibody 8C12 (blue) and anti-B220 (brown). (C and D) Staining was with PNA (blue) and anti-B220 (brown). Original magnification, ×100.
Mentions: TNFR-I–deficient mice also lack FDC clusters and spleen GC formation (25, 26). To investigate the mechanism of this structural defect in the TNFR-I–deficient mice, we performed similar reciprocal BM transfer experiments. In contrast to the LT-α–deficient mice, reconstitution of TNFR-I–deficient mice with wild-type BM did not restore the organization of FDC clusters or the formation of GC (Fig. 3, A and C). This suggests that development of normal clusters of FDC in the spleen requires TNFR-I expression on some radioresistant non–BM-derived component(s) in the recipient mouse, most likely a cellular element within the spleen itself. Alternatively, the failure to restore FDC clusters in TNFR-I–deficient mice after transfer of normal BM might indicate that essential TNFR-I–dependent interactions may be required within a developmental window before 8–12 wk of age, when these BM transfers were performed.

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