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Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice.

Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK - J. Exp. Med. (1997)

Bottom Line: The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR)-alpha-/- mice was explored by creating double mutant mice (TCR-alpha-/- x immunoglobulin (Ig)mu-/-), which lack B cells.Administration of the purified Ig from TCR-alpha-/- mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-alpha-/- x Ig mu-/- mice.These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells.

View Article: PubMed Central - PubMed

Affiliation: Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.

ABSTRACT
The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR)-alpha-/- mice was explored by creating double mutant mice (TCR-alpha-/- x immunoglobulin (Ig)mu-/-), which lack B cells. TCR-alpha-/- x Ig mu-/- mice spontaneously developed colitis at an earlier age, and the colitis was more severe than in TCR-alpha-/- mice. Colitis was induced in recombination-activating gene-1 (RAG-1-/-) mice by the transfer of mesenteric lymph node (MLN) cells from TCR-alpha-/- x Ig mu-/- mice. When purified B cells from TCR-alpha-/- mice were mixed with MLN cells before cell transfer, colitis did not develop in RAG-1-/- mice. Administration of the purified Ig from TCR-alpha-/- mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-alpha-/- x Ig mu-/- mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-alpha-/- x Ig mu-/- mice as compared to Ig mu-/- mice and TCR-alpha-/- mice. Administration of the purified Ig from TCR-alpha-/- mice into TCR-alpha-/- x Ig mu-/- mice led to decrease in the number of apoptotic cells. These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells.

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Apoptotic cells in the colon (top) and spleen (bottom) of Igμ−/−, TCR-α−/−, and TCR-α−/− × Igμ−/− mice injected with PBS or Ig purified from sera of TCR-α−/− mice were detected by TUNEL assay (×20 objective). All mice were 8 wk of age. The numbers in the right lower corner  indicate the number of apoptotic cells per mm2.
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Figure 5: Apoptotic cells in the colon (top) and spleen (bottom) of Igμ−/−, TCR-α−/−, and TCR-α−/− × Igμ−/− mice injected with PBS or Ig purified from sera of TCR-α−/− mice were detected by TUNEL assay (×20 objective). All mice were 8 wk of age. The numbers in the right lower corner indicate the number of apoptotic cells per mm2.

Mentions: Apoptotic bodies comprise the major source of autoAgs and provide powerful immunogens for autoreactive T cells (35, 36). Translocation of intracytoplasmic autoantigens to cell surface during apoptosis (37) indicates that autoAbs (ANCA) can bind intracytoplasmic Ags in the apoptotic process. It has been postulated that rapid clearance of apoptotic bodies by macrophages can prevent tissue damage caused by the harmful exposure to self Ags (38, 39). Therefore, to investigate the suppressive role of autoAbs in spontaneous colitis, apoptotic cells were enumerated by TUNEL assay (Fig. 5). TUNEL assay revealed marked increase in the number of apoptotic cells in the colon (epithelial cells and lamina propria cells), MLN, and spleen of TCR-α−/− × Igμ−/− mice compared to TCR-α−/− and Igμ−/− mice. However, when TCR-α−/− × Igμ−/− mice received passively transferred Ig from TCR-α−/− mice, the number of detectable apoptotic cells strikingly decreased. We also examined the expression of Fas, Fas ligand, bcl-2, and IL-1β converting enzymes (ICE) in the colon by immunohistochemical analysis, FACScan®, and/or reverse transcriptase PCR. There was no detectable difference in the expression of the molecules involved in apoptosis between the TCR-α−/− × Igμ−/− mice and TCR-α−/− mice (data not shown). This suggests that the increase in the number of apoptotic cells in TCR-α−/− × Igμ−/− mice is caused by alteration in the clearance of apoptotic cells rather than due to increase in apoptosis.


Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice.

Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK - J. Exp. Med. (1997)

Apoptotic cells in the colon (top) and spleen (bottom) of Igμ−/−, TCR-α−/−, and TCR-α−/− × Igμ−/− mice injected with PBS or Ig purified from sera of TCR-α−/− mice were detected by TUNEL assay (×20 objective). All mice were 8 wk of age. The numbers in the right lower corner  indicate the number of apoptotic cells per mm2.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2199135&req=5

Figure 5: Apoptotic cells in the colon (top) and spleen (bottom) of Igμ−/−, TCR-α−/−, and TCR-α−/− × Igμ−/− mice injected with PBS or Ig purified from sera of TCR-α−/− mice were detected by TUNEL assay (×20 objective). All mice were 8 wk of age. The numbers in the right lower corner indicate the number of apoptotic cells per mm2.
Mentions: Apoptotic bodies comprise the major source of autoAgs and provide powerful immunogens for autoreactive T cells (35, 36). Translocation of intracytoplasmic autoantigens to cell surface during apoptosis (37) indicates that autoAbs (ANCA) can bind intracytoplasmic Ags in the apoptotic process. It has been postulated that rapid clearance of apoptotic bodies by macrophages can prevent tissue damage caused by the harmful exposure to self Ags (38, 39). Therefore, to investigate the suppressive role of autoAbs in spontaneous colitis, apoptotic cells were enumerated by TUNEL assay (Fig. 5). TUNEL assay revealed marked increase in the number of apoptotic cells in the colon (epithelial cells and lamina propria cells), MLN, and spleen of TCR-α−/− × Igμ−/− mice compared to TCR-α−/− and Igμ−/− mice. However, when TCR-α−/− × Igμ−/− mice received passively transferred Ig from TCR-α−/− mice, the number of detectable apoptotic cells strikingly decreased. We also examined the expression of Fas, Fas ligand, bcl-2, and IL-1β converting enzymes (ICE) in the colon by immunohistochemical analysis, FACScan®, and/or reverse transcriptase PCR. There was no detectable difference in the expression of the molecules involved in apoptosis between the TCR-α−/− × Igμ−/− mice and TCR-α−/− mice (data not shown). This suggests that the increase in the number of apoptotic cells in TCR-α−/− × Igμ−/− mice is caused by alteration in the clearance of apoptotic cells rather than due to increase in apoptosis.

Bottom Line: The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR)-alpha-/- mice was explored by creating double mutant mice (TCR-alpha-/- x immunoglobulin (Ig)mu-/-), which lack B cells.Administration of the purified Ig from TCR-alpha-/- mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-alpha-/- x Ig mu-/- mice.These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells.

View Article: PubMed Central - PubMed

Affiliation: Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.

ABSTRACT
The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR)-alpha-/- mice was explored by creating double mutant mice (TCR-alpha-/- x immunoglobulin (Ig)mu-/-), which lack B cells. TCR-alpha-/- x Ig mu-/- mice spontaneously developed colitis at an earlier age, and the colitis was more severe than in TCR-alpha-/- mice. Colitis was induced in recombination-activating gene-1 (RAG-1-/-) mice by the transfer of mesenteric lymph node (MLN) cells from TCR-alpha-/- x Ig mu-/- mice. When purified B cells from TCR-alpha-/- mice were mixed with MLN cells before cell transfer, colitis did not develop in RAG-1-/- mice. Administration of the purified Ig from TCR-alpha-/- mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-alpha-/- x Ig mu-/- mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-alpha-/- x Ig mu-/- mice as compared to Ig mu-/- mice and TCR-alpha-/- mice. Administration of the purified Ig from TCR-alpha-/- mice into TCR-alpha-/- x Ig mu-/- mice led to decrease in the number of apoptotic cells. These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells.

Show MeSH
Related in: MedlinePlus