Limits...
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.

Show MeSH

Related in: MedlinePlus

Restoration of organized FDC clusters and GC in LT-α–deficient mice after transplantation with normal BM. After BM transfer, mice were immunized intraperitoneally with 100 μl of PBS containing 10% sheep red blood cells. 10 d later, spleens were harvested and frozen sections were stained  with (A–D) anti-CR1 antibody 8C12 (blue) and PNA (brown), or (E–H) with horseradish peroxidase–anti-peroxidase complex (brown) and anti-B220 (blue). (A  and E) LT-α–deficient mice reconstituted with wild-type BM showed restored FDC clusters and an ability to form GC. (B and F) Conversely, wild-type  mice reconstituted with LT-α–deficient BM showed no detectable FDC clusters or formation of GC. Wild-type mice reconstituted with wild-type BM (C  and G) and LT-α–deficient mice reconstituted with LT-α–deficient BM (D and H) showed similar anti-CR1 staining and in vitro IC trapping compared to  wild-type mice and LT-α–deficient mice, respectively. Original magnification, ×100.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199170&req=5

Figure 1: Restoration of organized FDC clusters and GC in LT-α–deficient mice after transplantation with normal BM. After BM transfer, mice were immunized intraperitoneally with 100 μl of PBS containing 10% sheep red blood cells. 10 d later, spleens were harvested and frozen sections were stained with (A–D) anti-CR1 antibody 8C12 (blue) and PNA (brown), or (E–H) with horseradish peroxidase–anti-peroxidase complex (brown) and anti-B220 (blue). (A and E) LT-α–deficient mice reconstituted with wild-type BM showed restored FDC clusters and an ability to form GC. (B and F) Conversely, wild-type mice reconstituted with LT-α–deficient BM showed no detectable FDC clusters or formation of GC. Wild-type mice reconstituted with wild-type BM (C and G) and LT-α–deficient mice reconstituted with LT-α–deficient BM (D and H) showed similar anti-CR1 staining and in vitro IC trapping compared to wild-type mice and LT-α–deficient mice, respectively. Original magnification, ×100.

Mentions: The role of LT-α in the organization of FDC was studied using reciprocal BM transfer experiments. 6–10 wk after BM transfer, FDC organization in these BM-chimeric mice was visualized immunohistochemically by using 8C12, an mAb specific for murine CR1 (39). LT-α–deficient mice reconstituted with normal BM demonstrated prominent FDC reticula in the GC light zones (Fig. 1 A). Similar results were obtained using the anti-FDC mAbs FDC-M1 and FDC-M2 (41) and 7G6 or 7E9, mAbs specific for murine CR1 and CR2 (data not shown). FDC organization was further assessed by analysis of IC trapping using spleen sections from these animals. Consistent with the result obtained from anti-CR1 staining, IC trapping was demonstrated at sites corresponding to the FDC reticula in these mice (Fig. 1 E). Thus, restoration of GC formation in wild-type BM-reconstituted LT-α–deficient mice was associated with de novo development of organized FDC structure. In contrast, wild-type mice reconstituted with LT-α–deficient BM showed no clusters of anti-CR1 staining cells or PNA+ cells (Fig. 1 B), and showed absence of IC trapping (Fig. 1 F). Wild-type mice reconstituted with wild-type BM (Fig. 1, C and G) and LT-α–deficient mice reconstituted with LT-α–deficient BM (Fig. 1, D and H) showed similar anti-CR1 staining and in vitro IC trapping compared to wild-type mice and LT-α–deficient mice, respectively.


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)

Restoration of organized FDC clusters and GC in LT-α–deficient mice after transplantation with normal BM. After BM transfer, mice were immunized intraperitoneally with 100 μl of PBS containing 10% sheep red blood cells. 10 d later, spleens were harvested and frozen sections were stained  with (A–D) anti-CR1 antibody 8C12 (blue) and PNA (brown), or (E–H) with horseradish peroxidase–anti-peroxidase complex (brown) and anti-B220 (blue). (A  and E) LT-α–deficient mice reconstituted with wild-type BM showed restored FDC clusters and an ability to form GC. (B and F) Conversely, wild-type  mice reconstituted with LT-α–deficient BM showed no detectable FDC clusters or formation of GC. Wild-type mice reconstituted with wild-type BM (C  and G) and LT-α–deficient mice reconstituted with LT-α–deficient BM (D and H) showed similar anti-CR1 staining and in vitro IC trapping compared to  wild-type mice and LT-α–deficient mice, respectively. Original magnification, ×100.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Restoration of organized FDC clusters and GC in LT-α–deficient mice after transplantation with normal BM. After BM transfer, mice were immunized intraperitoneally with 100 μl of PBS containing 10% sheep red blood cells. 10 d later, spleens were harvested and frozen sections were stained with (A–D) anti-CR1 antibody 8C12 (blue) and PNA (brown), or (E–H) with horseradish peroxidase–anti-peroxidase complex (brown) and anti-B220 (blue). (A and E) LT-α–deficient mice reconstituted with wild-type BM showed restored FDC clusters and an ability to form GC. (B and F) Conversely, wild-type mice reconstituted with LT-α–deficient BM showed no detectable FDC clusters or formation of GC. Wild-type mice reconstituted with wild-type BM (C and G) and LT-α–deficient mice reconstituted with LT-α–deficient BM (D and H) showed similar anti-CR1 staining and in vitro IC trapping compared to wild-type mice and LT-α–deficient mice, respectively. Original magnification, ×100.
Mentions: The role of LT-α in the organization of FDC was studied using reciprocal BM transfer experiments. 6–10 wk after BM transfer, FDC organization in these BM-chimeric mice was visualized immunohistochemically by using 8C12, an mAb specific for murine CR1 (39). LT-α–deficient mice reconstituted with normal BM demonstrated prominent FDC reticula in the GC light zones (Fig. 1 A). Similar results were obtained using the anti-FDC mAbs FDC-M1 and FDC-M2 (41) and 7G6 or 7E9, mAbs specific for murine CR1 and CR2 (data not shown). FDC organization was further assessed by analysis of IC trapping using spleen sections from these animals. Consistent with the result obtained from anti-CR1 staining, IC trapping was demonstrated at sites corresponding to the FDC reticula in these mice (Fig. 1 E). Thus, restoration of GC formation in wild-type BM-reconstituted LT-α–deficient mice was associated with de novo development of organized FDC structure. In contrast, wild-type mice reconstituted with LT-α–deficient BM showed no clusters of anti-CR1 staining cells or PNA+ cells (Fig. 1 B), and showed absence of IC trapping (Fig. 1 F). Wild-type mice reconstituted with wild-type BM (Fig. 1, C and G) and LT-α–deficient mice reconstituted with LT-α–deficient BM (Fig. 1, D and H) showed similar anti-CR1 staining and in vitro IC trapping compared to wild-type mice and LT-α–deficient mice, respectively.

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